Pål Falnes

• Falnes, Pål & Davydova, Erna (2026). The Protein Histidine Methyltransferase METTL9—From Mechanism to Biological Function. Life. 16(3). doi: 10.3390/life16030445. Full text in Research Archive
• Schroer, Lisa; Weirich, Sara; Hammerstad, Marta; Hersleth, Hans-Petter; Grønsberg, Ida Andrietta & Hagen, Lars [Show all 11 contributors for this article] (2025). Orthologues of the human protein histidine methyltransferase METTL9 display distinct substrate specificities. Journal of Biological Chemistry. ISSN 0021-9258. 301(7). doi: 10.1016/j.jbc.2025.110318. Full text in Research Archive Show summary

  The human (Homo sapiens; Hs) methyltransferase (MTase) METTL9 is the first enzyme shown to generate 1-methylhistidine (π-methylhistidine) in proteins. METTL9 preferentially methylates an alternating histidine (HxH) motif, where “x” is a small, uncharged amino acid, and multiple substrates have been identified. Putative METTL9 orthologues are found in most eukaryotes, and we have here investigated the activity of such enzymes from several species, representing all five eukaryotic supergroups. The majority of the tested enzymes demonstrated in vitro MTase activity on the prototype HsMETTL9 substrates ARMC6 and DNAJB12. We also detected protein methylation activity of the Caenorhabditis elegans METTL9 which had previously been suggested to be a DNA MTase. However, METTL9 from the fruit fly (Drosophila melanogaster; Dm) and the picoplankton Ostreococcus tauri (Ot) displayed distinct substrate specificities, differing from each other and from that of HsMETTL9. These differences were observed when recombinant proteins and short peptides were used as METTL9 substrates. To further analyze substrate specificity, we used peptide arrays to systematically replace the “x” residue and the residues flanking the HxH motif in a substrate peptide. This revealed varying degrees of tolerance among the METTL9 orthologues (Hs > Dm > Ot) for substitutions at these positions. Our results show that the METTL9 orthologues, although requiring an HxH target site, have evolved different substrate specificities, likely due to differing biologically relevant substrates in the respective organisms. Furthermore, we solved the X-ray structure of OtMETTL9, revealing several differences from the previously published HsMETTL9 structures that may explain its distinct substrate specificity.

• Malecki, Jedrzej Mieczyslaw; Weirich, Sara; Ramirez, Manuel; Hagen, Lars; Al-Egly, Jakin Saad & Anonsen, Jan Haug [Show all 12 contributors for this article] (2025). Identification of substrates and sequence requirements for CARNMT1-mediated histidine methylation of C3H zinc fingers. Journal of Biological Chemistry. ISSN 0021-9258. 301(7). doi: 10.1016/j.jbc.2025.110335. Full text in Research Archive Show summary

  It has recently become clear that protein histidine methylation is widespread and functionally important in many cellular processes, and human CARNMT1 was recently reported as a novel protein histidine methyltransferase (HMT). We describe our independent uncovering of CARNMT1's protein HMT activity and a comprehensive assessment of its methylation targets and substrate specificity. Using a combination of in vitro methylation of cellular extracts and protein mass spectrometry, we identified several CARNMT1 substrates that were fully methylated in cells, all of which were C3H zinc finger (ZnF) proteins. These include the previously identified U2AF1, ZC3H15, and ZC3H18 but also the unreported RBM22, PPP1R10, PRR3, and RNF113A. Using peptide arrays, we investigated CARNMT1-mediated methylation of 145 candidate sequences, encompassing all C3H ZnFs and selected non-ZnFs. We found that only ∼30% of the tested sequences were methylated, with C3H ZnFs constituting the vast majority of the strongly methylated ones, most of which are also methylated in cells. This establishes peptide methylation as a good predictor of in vivo methylation. To investigate the specificity of CARNMT1, we systematically substituted His-proximal residues in four different substrate peptides. This generated four rather different sequence preference profiles, which were still quite restrictive for each peptide, indicating that substrate sequence recognition by CARNMT1 is context-dependent and that sequence-based prediction of additional CARNMT1 substrates may be challenging. We also identified several homologous methylation events in Caenorhabditis elegans and showed that they could be introduced by nematode CARNMT in vitro. Thus, CARNMT1 is an evolutionarily conserved protein HMT with a complex mode of substrate recognition.

• Falnes, Pål (2024). Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases. Nucleic Acids Research (NAR). ISSN 0305-1048. 52(19), p. 11423–11441. doi: 10.1093/nar/gkae816. Full text in Research Archive Show summary

  Methylation is a common biochemical reaction, and a number of methyltransferase (MTase) enzymes mediate the various methylation events occurring in living cells. Almost all MTases use the methyl donor S-adenosylmethionine (AdoMet), and, in humans, the largest group of AdoMet-dependent MTases are the so-called seven-β-strand (7BS) MTases. Collectively, the 7BS MTases target a wide range of biomolecules, i.e. nucleic acids and proteins, as well as several small metabolites and signaling molecules. They play essential roles in key processes such as gene regulation, protein synthesis and metabolism, as well as neurotransmitter synthesis and clearance. A decade ago, roughly half of the human 7BS MTases had been characterized experimentally, whereas the remaining ones merely represented hypothetical enzymes predicted from bioinformatics analysis, many of which were denoted METTLs (METhylTransferase-Like). Since then, considerable progress has been made, and the function of > 80% of the human 7BS MTases has been uncovered. In this review, I provide an overview of the (estimated) 120 human 7BS MTases, grouping them according to substrate specificities and sequence similarity. I also elaborate on the challenges faced when studying these enzymes and describe recent major advances in the field.

• Willemen, Hanneke L.D.M.; Ribeiro, Patrícia Silva Santos; Broeks, Melissa; Meijer, Nils; Versteeg, Sabine & Tiggeler, Annefien [Show all 11 contributors for this article] (2023). Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain. Cell Reports Medicine. 4(11), p. 1–24. doi: 10.1016/j.xcrm.2023.101265. Full text in Research Archive Show summary

  Pain often persists in patients with an inflammatory disease, even when inflammation has subsided. The molecular mechanisms leading to this failure in pain resolution and the transition to chronic pain are poorly understood. Mitochondrial dysfunction in sensory neurons links to chronic pain, but its role in resolution of inflammatory pain is unclear. Transient inflammation causes neuronal plasticity, called hyperalgesic priming, which impairs resolution of pain induced by a subsequent inflammatory stimulus. We identify that hyperalgesic priming in mice increases the expression of a mitochondrial protein (ATPSc-KMT) and causes mitochondrial and metabolic disturbances in sensory neurons. Inhibition of mitochondrial respiration, knockdown of ATPSCKMT expression, or supplementation of the affected metabolite is sufficient to restore resolution of inflammatory pain and prevents chronic pain development. Thus, inflammation-induced mitochondrial-dependent disturbances in sensory neurons predispose to a failure in resolution of inflammatory pain and development of chronic pain.

• Falnes, Pål; Malecki, Jedrzej Mieczyslaw; Gonzalez-Molina, Maria del Carmen Herrera; Bengtsen, Mads & Davydova, Erna (2023). Human seven-β-strand (METTL) methyltransferases - conquering the universe of protein lysine methylation. Journal of Biological Chemistry. ISSN 0021-9258. 299(6), p. 1–15. doi: 10.1016/j.jbc.2023.104661. Full text in Research Archive Show summary

  Lysine methylation is an abundant posttranslational modification, which has been most intensively studied in the context of histone proteins, where it represents an important epigenetic mark. Lysine methylation of histone proteins is primarily catalyzed by SET-domain methyltransferases (MTases). However, it has recently become evident that also another MTase family, the so-called seven-β-strand (7BS) MTases, often denoted METTLs (methyltransferase-like), contains several lysine (K)-specific MTases (KMTs). These enzymes catalyze the attachment of up to three methyl groups to lysine residues in specific substrate proteins, using S-adenosylmethionine (AdoMet) as methyl donor. About a decade ago, only a single human 7BS KMT was known, namely the histone-specific DOT1L, but 15 additional 7BS KMTs have now been discovered and characterized. These KMTs typically target a single nonhistone substrate that, in most cases, belongs to one of the following three protein groups: components of the cellular protein synthesis machinery, mitochondrial proteins, and molecular chaperones. This article provides an extensive overview and discussion of the human 7BS KMTs and their biochemical and biological roles.

• Engelfriet, Melanie Lianne; Malecki, Jedrzej Mieczyslaw; Forsberg, Frida; Falnes, Pål & Ciosk, Rafal (2023). Characterization of the biochemical activity and tumor-promoting role of the dual protein methyltransferase METL-13/METTL13 in Caenorhabditis elegans. PLOS ONE. 18(6), p. 1–16. doi: 10.1371/journal.pone.0287558. Full text in Research Archive Show summary

  The methyltransferase-like protein 13 (METTL13) methylates the eukaryotic elongation factor 1 alpha (eEF1A) on two locations: the N-terminal amino group and lysine 55. The absence of this methylation leads to reduced protein synthesis and cell proliferation in human cancer cells. Previous studies showed that METTL13 is dispensable in non-transformed cells, making it potentially interesting for cancer therapy. However, METTL13 has not been examined yet in whole animals. Here, we used the nematode Caenorhabditis elegans as a simple model to assess the functions of METTL13. Using methyltransferase assays and mass spectrometry, we show that the C . elegans METTL13 (METL-13) methylates eEF1A (EEF-1A) in the same way as the human protein. Crucially, the cancer-promoting role of METL-13 is also conserved and depends on the methylation of EEF-1A, like in human cells. At the same time, METL-13 appears dispensable for animal growth, development, and stress responses. This makes C . elegans a convenient whole-animal model for studying METL13-dependent carcinogenesis without the complications of interfering with essential wild-type functions.

• Malecki, Jedrzej Mieczyslaw; Davydova, Erna & Falnes, Pål (2022). Protein methylation in mitochondria. Journal of Biological Chemistry. ISSN 0021-9258. 298(4). doi: 10.1016/j.jbc.2022.101791. Full text in Research Archive Show summary

  Many proteins are modified by posttranslational methylation, introduced by a number of methyltransferases (MTases). Protein methylation plays important roles in modulating protein function and thus in optimizing and regulating cellular and physiological processes. Research has mainly focused on nuclear and cytosolic protein methylation, but it has been known for many years that also mitochondrial proteins are methylated. During the last decade, significant progress has been made on identifying the MTases responsible for mitochondrial protein methylation and addressing its functional significance. In particular, several novel human MTases have been uncovered that methylate lysine, arginine, histidine, and glutamine residues in various mitochondrial substrates. Several of these substrates are key components of the bioenergetics machinery, e.g., respiratory Complex I, citrate synthase, and the ATP synthase. In the present review, we report the status of the field of mitochondrial protein methylation, with a particular emphasis on recently discovered human MTases. We also discuss evolutionary aspects and functional significance of mitochondrial protein methylation and present an outlook for this emergent research field.

• Malecki, Jedrzej Mieczyslaw; O'Donohue, Marie-Francoise; Kim, Yeji; Jakobsson, Magnus; Gessa, Luca & Pinto, Rita [Show all 14 contributors for this article] (2021). Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function. Nucleic Acids Research (NAR). ISSN 0305-1048. 49(6), p. 3185–3203. doi: 10.1093/nar/gkab088. Full text in Research Archive Show summary

  Abstract Protein methylation occurs primarily on lysine and arginine, but also on some other residues, such as histidine. METTL18 is the last uncharacterized member of a group of human methyltransferases (MTases) that mainly exert lysine methylation, and here we set out to elucidate its function. We found METTL18 to be a nuclear protein that contains a functional nuclear localization signal and accumulates in nucleoli. Recombinant METTL18 methylated a single protein in nuclear extracts and in isolated ribosomes from METTL18 knockout (KO) cells, identified as 60S ribosomal protein L3 (RPL3). We also performed an RPL3 interactomics screen and identified METTL18 as the most significantly enriched MTase. We found that His-245 in RPL3 carries a 3-methylhistidine (3MH; τ-methylhistidine) modification, which was absent in METTL18 KO cells. In addition, both recombinant and endogenous METTL18 were found to be automethylated at His-154, thus further corroborating METTL18 as a histidine-specific MTase. Finally, METTL18 KO cells displayed altered pre-rRNA processing, decreased polysome formation and codon-specific changes in mRNA translation, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function. In conclusion, we have here established METTL18 as the second human histidine-specific protein MTase, and demonstrated its functional relevance.

• Davydova, Erna; Shimazu, Tadahiro; Schuhmacher, Maren Kirstin; Jakobsson, Magnus E.; Willemen, Hanneke L.D.M. & Liu, Tongri [Show all 28 contributors for this article] (2021). The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes. Nature Communications. 12, p. 1–14. doi: 10.1038/s41467-020-20670-7. Full text in Research Archive Show summary

  Abstract Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.

• Malecki, Jedrzej Mieczyslaw; Willemen, Hanneke L.D.M.; Pinto, Rita; Ho, Angela Yeuan Yen; Moen, Anders & Eijkelkamp, Niels [Show all 7 contributors for this article] (2019). Human FAM173A is a mitochondrial lysine-specific methyltransferase that targets adenine nucleotide translocase and affects mitochondrial respiration. Journal of Biological Chemistry. ISSN 0021-9258. 294(31), p. 11654–11664. doi: 10.1074/jbc.RA119.009045. Full text in Research Archive
• Pinto, Rita; Vågbø, Cathrine Broberg; Jakobsson, Magnus; Yeji, Kim; Baltissen, Marijke P & O'Donohue, Marie-Francoise [Show all 16 contributors for this article] (2019). The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. Nucleic Acids Research (NAR). ISSN 0305-1048. 48(2), p. 830–846. doi: 10.1093/nar/gkz1147. Full text in Research Archive Show summary

  RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem–loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.

• Malecki, Jedrzej Mieczyslaw; Willemen, Hanneke L.D.M.; Pinto, Rita; Ho, Angela Yeuan Yen; Moen, Anders & Kjønstad, Ingrid Fadum [Show all 10 contributors for this article] (2018). Lysine methylation by the mitochondrial methyltransferase FAM173B optimizes the function of mitochondrial ATP synthase. Journal of Biological Chemistry. ISSN 0021-9258. 294(4), p. 1128–1141. doi: 10.1074/jbc.RA118.005473. Full text in Research Archive Show summary

  Lysine methylation is an important post-translational modification that is also present on mitochondrial proteins, but the mitochondrial lysine-specific methyltransferases (KMTs) responsible for modification are in most cases unknown. Here, we set out to determine the function of human family with sequence similarity 173 member B (FAM173B), a mitochondrial methyltransferase (MTase) reported to promote chronic pain. Using bioinformatics analyses and biochemical assays, we found that FAM173B contains an atypical, noncleavable mitochondrial targeting sequence responsible for its localization to mitochondria. Interestingly, CRISPR/Cas9-mediated KO of FAM173B in mammalian cells abrogated trimethylation of Lys-43 in ATP synthase c-subunit (ATPSc), a modification previously reported as ubiquitous among metazoans. ATPSc methylation was restored by complementing the KO cells with enzymatically active human FAM173B or with a putative FAM173B orthologue from the nematode Caenorhabditis elegans. Interestingly, lack of Lys-43 methylation caused aberrant incorporation of ATPSc into the ATP synthase complex and resulted in decreased ATP-generating ability of the complex, as well as decreased mitochondrial respiration. In summary, we have identified FAM173B as the long-sought KMT responsible for methylation of ATPSc, a key protein in cellular ATP production, and have demonstrated functional significance of ATPSc methylation. We suggest renaming FAM173B to ATPSc-KMT (gene name ATPSCKMT).

• Jakobsson, Magnus; Malecki, Jedrzej Mieczyslaw & Falnes, Pål Øystein (2018). Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation. RNA Biology. ISSN 1547-6286. 15(3), p. 314–319. doi: 10.1080/15476286.2018.1440875. Full text in Research Archive
• Jakobsson, Magnus; Malecki, Jedrzej Mieczyslaw; Halabelian, Levon; Nilges, Benedikt S.; Pinto, Rita & Kudithipudi, Srikanth [Show all 14 contributors for this article] (2018). The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates. Nature Communications. 9:3411, p. 1–15. doi: 10.1038/s41467-018-05646-y. Full text in Research Archive Show summary

  Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

• Willemen, Hanneke L.D.M.; Kavelaars, Annemieke; Prado, Judith; Maas, MIrjam; Versteeg, Sabine & Nellissen, Lara J.J. [Show all 16 contributors for this article] (2018). Identification of FAM173B as a protein methyltransferase promoting chronic pain. PLoS Biology. ISSN 1544-9173. 16(2). doi: 10.1371/journal.pbio.2003452. Full text in Research Archive
• Malecki, Jedrzej Mieczyslaw; Jakobsson, Magnus; Ho, Angela Yeuan Yen; Moen, Anders; Rustan, Arild & Falnes, Pål (2017). Uncovering human METTL12 as a mitochondrial methyltransferase that modulates citrate synthase activity through metabolite-sensitive lysine methylation. Journal of Biological Chemistry. ISSN 0021-9258. 292(43), p. 17950–17962. doi: 10.1074/jbc.M117.808451. Full text in Research Archive Show summary

  Lysine methylation is an important and much-studied posttranslational modification of nuclear and cytosolic proteins but is present also in mitochondria. However, the responsible mitochondrial lysine-specific methyltransferases (KMTs) remain largely elusive. Here, we investigated METTL12, a mitochondrial human S-adenosylmethionine (AdoMet)-dependent methyltransferase and found it to methylate a single protein in mitochondrial extracts, identified as citrate synthase (CS). Using several in vitro and in vivo approaches, we demonstrated that METTL12 methylates CS on Lys-395, which is localized in the CS active site. Interestingly, the METTL12-mediated methylation inhibited CS activity and was blocked by the CS substrate oxaloacetate. Moreover, METTL12 was strongly inhibited by the reaction product S-adenosylhomocysteine (AdoHcy). In summary, we have uncovered a novel human mitochondrial KMT that introduces a methyl modification into a metabolic enzyme and whose activity can be modulated by metabolic cues. Based on the established naming nomenclature for similar enzymes, we suggest that METTL12 be renamed CS-KMT (gene name CSKMT). This research was originally published in the Journal of Biological Chemistry. © 2017 American Society for Biochemistry and Molecular Biology

• Malecki, Jedrzej Mieczyslaw; Aileni, Vinay Kumar; Ho, Angela Yeuan Yen; Schwarz, Juliane; Moen, Anders & Sørensen, Vigdis [Show all 10 contributors for this article] (2017). The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A). Nucleic Acids Research (NAR). ISSN 0305-1048. 45(8), p. 4370–4389. doi: 10.1093/nar/gkx002. Full text in Research Archive Show summary

  Lysine methylation is abundant on histone proteins, representing a dynamic regulator of chromatin state and gene activity, but is also frequent on many nonhistone proteins, including eukaryotic elongation factor 1 alpha (eEF1A). However, the functional significance of eEF1Amethylation remains obscure and it has remained unclear whether eEF1A methylation is dynamic and subject to active regulation. We here demonstrate, using a wide range of in vitro and in vivo approaches, that the previously uncharacterized human methyltransferase METTL21B specifically targets Lys-165 in eEF1A in an aminoacyl-tRNA- and GTP-dependent manner. Interestingly, METTL21B mediated eEF1A methylation showed strong variation across different tissues and cell lines, and was induced by altering growth conditions or by treatment with certain ER-stress-inducing drugs, concomitant with an increase in METTL21B gene expression. Moreover, genetic ablation of METTL21B function in mammalian cells caused substantial alterations in mRNA translation, as measured by ribosomal profiling. A non-canonical function for eEF1A in organization of the cellular cytoskeleton has been reported, and interestingly, METTL21B accumulated in centrosomes, in addition to the expected cytosolic localization. In summary, the present study identifies METTL21B as the enzyme responsible for methylation of eEF1A on Lys-165 and shows that this modification is dynamic, inducible and likely of regulatory importance.

• Jakobsson, Magnus; Malecki, Jedrzej Mieczyslaw; Nilges, Benedikt S.; Moen, Anders; Leidel, Sebastian A. & Falnes, Pål (2017). Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation. Nucleic Acids Research (NAR). ISSN 0305-1048. 45, p. 8239–8254. doi: 10.1093/nar/gkx432. Full text in Research Archive Show summary

  Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-β-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme. Combining in vitro enzymology and analyzes of knockout cells, we demonstrate that this MTase efficiently methylates K36 in eukaryotic translation elongation factor 1 alpha (eEF1A) in vitro and in vivo. We suggest that this novel KMT is named eEF1A-KMT4 (gene name EEF1AKMT4), in agreement with the recently established nomenclature. Furthermore, by ribosome profiling we show that the absence of K36 methylation affects translation dynamics and changes translation speed of distinct codons. Finally, we show that eEF1A-KMT4 is part of a novel family of human KMTs, defined by a shared sequence motif in the active site and we demonstrate the importance of this motif for catalytic activity.

• Aileni, Vinay Kumar; Davydova, Erna; Moen, Anders & Falnes, Pål (2017). A System for Enzymatic Lysine Methylation in a Desired Sequence Context. ACS Omega. 2(2), p. 462–469. doi: 10.1021/acsomega.6b00486. Full text in Research Archive Show summary

  A number of lysine-specific methyltransferases (KMTs) are responsible for the post-translational modification of cellular proteins on lysine residues. Most KMTs typically recognize specific motifs in unstructured, short peptide sequences. However, we have recently discovered a novel KMT that appeared to have a more relaxed sequence specificity, namely, valosin-containing protein (VCP)-KMT, which trimethylates Lys-315 in the molecular chaperone VCP. On the basis of this, here, we explored the possibility of using the VCP-KMT/VCP system to obtain specific lysine methylation of desired sequences grafted onto a VCP-derived scaffold. We generated VCP-derived proteins in which three amino acid residues on each side of Lys-315 had been replaced by various sequences representing lysine methylation sites in histone H3. We found that all of these chimeric proteins were subject to efficient VCP-KMT-mediated methylation in vitro, and methylation was also observed in mammalian cells. Thus, we here describe a versatile system for introducing lysine methylation into a desired peptide sequence, and the approach should be readily expandable for generating combinatorial libraries of methylated sequences.

• Falnes, Pål; Jakobsson, Magnus; Davydova, Erna; Ho, Angela Yeuan Yen & Malecki, Jedrzej Mieczyslaw (2016). Protein lysine methylation by seven-β-strand methyltransferases. Biochemical Journal. ISSN 0264-6021. 473(14), p. 1995–2009. doi: 10.1042/BCJ20160117. Full text in Research Archive
• Malecki, Jedrzej Mieczyslaw; Dahl, Helge-Andre; Moen, Anders; Davydova, Erna & Falnes, Pål (2016). The METTL20 homologue from agrobacterium tumefaciens is a dual specificity protein-lysine methyltransferase that targets ribosomal protein L7/L12 and the β subunit of electron transfer flavoprotein (ETFβ). Journal of Biological Chemistry. ISSN 0021-9258. 291(18), p. 9581–9595. doi: 10.1074/jbc.M115.709261. Full text in Research Archive
• Jakobsson, Magnus; Davydova, Erna; Malecki, Jedrzej Mieczyslaw; Moen, Anders & Falnes, Pål (2015). Saccharomyces cerevisiae eukaryotic elongation factor 1A (eEF1A) is methylated at Lys-390 by a METTL21-like methyltransferase. PLOS ONE. 10(6). doi: 10.1371/journal.pone.0131426. Full text in Research Archive Show summary

  The human methyltransferases (MTases) METTL21A and VCP-KMT (METTL21D) were recently shown to methylate single lysine residues in Hsp70 proteins and in VCP, respectively. The yet uncharacterized MTase encoded by the YNL024C gene in Saccharomyces cerevisiae shows high sequence similarity to METTL21A and VCP-KMT, as well as to their uncharacterized paralogues METTL21B and METTL21C. Despite being most similar to METTL21A, the Ynl024c protein does not methylate yeast Hsp70 proteins, which were found to be unmethylated on the relevant lysine residue. Eukaryotic translation elongation factor eEF1A in yeast has been reported to contain four methylated lysine residues (Lys30, Lys79, Lys318 and Lys390), and we here show that the YNL024C gene is required for methylation of eEF1A at Lys390, the only of these methylations for which the responsible MTase has not yet been identified. Lys390 was found in a partially monomethylated state in wild-type yeast cells but was exclusively unmethylated in a ynl024cΔ strain, and over-expression of Ynl024c caused a dramatic increase in Lys390 methylation, with trimethylation becoming the predominant state. Our results demonstrate that Ynl024c is the enzyme responsible for methylation of eEF1A at Lys390, and in accordance with prior naming of similar enzymes, we suggest that Ynl024c is renamed to Efm6 (Elongation factor MTase 6).

• Fusser, Markus; Kernstock, Stefan; Aileni, Vinay Kumar; Jacobsen, Wolfgang Mathias; Falnes, Pål & Klungland, Arne (2015). Lysine methylation of the valosin-containing protein (VCP) is dispensable for development and survival of mice. PLOS ONE. 10(11). doi: 10.1371/journal.pone.0141472. Full text in Research Archive
• Malecki, Jedrzej Mieczyslaw; Ho, Angela Yeuan Yen; Moen, Anders; Dahl, Helge-Andre & Falnes, Pål (2015). Human METTL20 is a mitochondrial lysine methyltransferase that targets the β subunit of electron transfer flavoprotein (ETFβ) and modulates its activity. Journal of Biological Chemistry. ISSN 0021-9258. 290(1), p. 423–434. doi: 10.1074/jbc.M114.614115. Full text in Research Archive
• Zdzalik, Daria; Domanska, Anna; Prorok, Paulina; Kosicki, Konrad; Born, Erwin Van den & Falnes, Pål [Show all 9 contributors for this article] (2015). Differential repair of etheno-DNA adducts by bacterial and human AlkB proteins. DNA Repair. ISSN 1568-7864. 30, p. 1–10. doi: 10.1016/j.dnarep.2015.02.021. Full text in Research Archive
• Jakobsson, Magnus; Moen, Anders; Davidson, Ben & Falnes, Pål (2015). Hsp70 (HSPA1) lysine methylation status as a potential prognostic factor in metastatic high-grade serous carcinoma. PLOS ONE. 10:e0140168(10). doi: 10.1371/journal.pone.0140168. Full text in Research Archive Show summary

  Cellular proteins are subject to frequent methylation on lysine residues, introduced by specific methyltransferases, and each lysine residue can receive up to three methyl groups. Histone methylations, which are key determinants of chromatin state and transcriptional status, have been subject to particularly intense studies, but methylations on non-histone protein substrates are also abundant and biologically significant. Numerous studies have addressed lysine methylation in the realm of cancer biology. A recent study used an antibody-based approach to investigate the methylation of Lys-561 of the stress-inducible Hsp70 protein HSPA1, focusing exclusively on dimethylated HSPA1, concluding that it was elevated in cancer [Cho et al. (2012), Nat. Commun.,3, 1072]. In the present study, we have performed a more extensive analysis of HSPA1 methylation status in cancer samples, using protein mass spectrometry. We found that the four methylation states of Lys561 on HSPA1 (un-, mono-, di- and trimethylated) could be measured accurately and reproducibly in samples from carcinomas. We investigated HSPA1 methylation in 70 effusions, representing 53 high-grade serous ovarian carcinomas and 17 breast carcinomas. Notably, we found the trimethylated form of HSPA1 to be predominant in the cancer samples. HSPA1 methylation was studied for association with clinicopathologic parameters, including chemotherapy response and survival. The trimethylated form was more prevalent in breast carcinoma effusions (p = 0.014), whereas the dimethylated (p = 0.025), monomethylated (p = 0.004) and unmethylated (p = 0.021) forms were overrepresented in the ovarian carcinomas. For the ovarian carcinomas, the monomethylated (p = 0.028) and unmethylated (p = 0.007) forms were significantly related to the presence of higher residual disease volume, while the unmethylated form was significantly associated with poor overall (p = 0.015) and progression-free (p = 0.012) survival. In conclusion, lysine methylation of HSPA1 differs between metastatic breast and ovarian carcinoma, and unmethylated HSPA1 shows potential as a prognostic marker in high-grade serous carcinoma.

• Zdzalik, Daria; Vågbø, Cathrine Broberg; Kirpekar, F; Davydova, Erna; Puścian, Alicja & Maciejewska, Agnieszka M. [Show all 11 contributors for this article] (2014). Protozoan ALKBH8 Oxygenases Display both DNA Repair and tRNA Modification Activities. PLOS ONE. 9(6). doi: 10.1371/journal.pone.0098729. Full text in Research Archive Show summary

  The ALKBH family of Fe(II) and 2-oxoglutarate dependent oxygenases comprises enzymes that display sequence homology to AlkB from E. coli, a DNA repair enzyme that uses an oxidative mechanism to dealkylate methyl and etheno adducts on the nucleobases. Humans have nine different ALKBH proteins, ALKBH1–8 and FTO. Mammalian and plant ALKBH8 are tRNA hydroxylases targeting 5-methoxycarbonylmethyl-modified uridine (mcm5U) at the wobble position of tRNAGly(UCC). In contrast, the genomes of some bacteria encode a protein with strong sequence homology to ALKBH8, and robust DNA repair activity was previously demonstrated for one such protein. To further explore this apparent functional duality of the ALKBH8 proteins, we have here enzymatically characterized a panel of such proteins, originating from bacteria, protozoa and mimivirus. All the enzymes showed DNA repair activity in vitro, but, interestingly, two protozoan ALKBH8s also catalyzed wobble uridine modification of tRNA, thus displaying a dual in vitro activity. Also, we found the modification status of tRNAGly(UCC) to be unaltered in an ALKBH8 deficient mutant of Agrobacterium tumefaciens, indicating that bacterial ALKBH8s have a function different from that of their eukaryotic counterparts. The present study provides new insights on the function and evolution of the ALKBH8 family of proteins.

• Davydova, Erna; Ho, Angela Yeuan Yen; Malecki, Jedrzej Mieczyslaw; Moen, Anders; Enserink, Jorrit & Jakobsson, Magnus [Show all 8 contributors for this article] (2014). Identification and characterization of a novel evolutionarily conserved lysine-specific methyltransferase targeting eukaryotic translation elongation factor 2 (eEF2). Journal of Biological Chemistry. ISSN 0021-9258. 289(44), p. 30499–30510. doi: 10.1074/jbc.M114.601658. Full text in Research Archive
• Lin, Fu-Jung; Shen, Li; Jang, Chuan-Wei; Falnes, Pål & Zhang, Yi (2013). Ikbkap/Elp1 Deficiency Causes Male Infertility by Disrupting Meiotic Progression. PLoS Genetics. ISSN 1553-7390. 9(5). doi: 10.1371/journal.pgen.1003516. Full text in Research Archive
• Jakobsson, Magnus; Moen, Anders; Bousset, Luc; Jacobsen, Wolfgang Mathias; Kernstock, Jens Stefan & Melki, Ronald [Show all 7 contributors for this article] (2013). Identification and characterization of a novel human methyltransferase modulating hsp70 Protein function through lysine methylation. Journal of Biological Chemistry. ISSN 0021-9258. 288(39), p. 27752–27763. doi: 10.1074/jbc.M113.483248. Full text in Research Archive
• Meza, Trine Johansen; Moen, Marivi; Vågbø, Cathrine Broberg; Krokan, Hans Einar; Klungland, Arne & Grini, Paul Eivind [Show all 7 contributors for this article] (2012). The DNA dioxygenase ALKBH2 protects Arabidopsis thaliana against methylation damage. Nucleic Acids Research (NAR). ISSN 0305-1048. 40(14), p. 6620–6631. doi: 10.1093/nar/gks327. Full text in Research Archive Show summary

  The Escherichia coli AlkB protein (EcAlkB) is a DNA repair enzyme which reverses methylation damage such as 1-methyladenine (1-meA) and 3-methylcytosine (3-meC). The mammalian AlkB homologues ALKBH2 and ALKBH3 display EcAlkB-like repair activity in vitro , but their substrate specificities are different, and ALKBH2 is the main DNA repair enzyme for 1-meA in vivo . The genome of the model plant Arabidopsis thaliana encodes several AlkB homologues, including the yet uncharacterized protein AT2G22260, which displays sequence similarity to both ALKBH2 and ALKBH3. We have here characterized protein AT2G22260, by us denoted ALKBH2, as both our functional studies and bioinformatics analysis suggest it to be an orthologue of mammalian ALKBH2. The Arabidopsis ALKBH2 protein displayed in vitro repair activities towards methyl and etheno adducts in DNA, and was able to complement corresponding repair deficiencies of the E. coli alkB mutant. Interestingly, alkbh2 knock-out plants were sensitive to the methylating agent methylmethanesulphonate (MMS), and seedlings from these plants developed abnormally when grown in the presence of MMS. The present study establishes ALKBH2 as an important enzyme for protecting Arabidopsis against methylation damage in DNA, and suggests its homologues in other plants to have a similar function.

• Kernstock, Jens Stefan; Davydova, Erna; Jakobsson, Magnus; Moen, Anders; Pettersen, Solveig & Mælandsmo, Gunhild [Show all 8 contributors for this article] (2012). Lysine methylation of VCP by a member of a novel human protein methyltransferase family. Nature Communications. 3. doi: 10.1038/ncomms2041. Full text in Research Archive
• Bjørnstad, Linn; Meza, Trine Johansen; Otterlei, Marit; Olafsrud, Solveig Mjelstad; Meza-Zepeda, Leonardo Andrés & Falnes, Pål (2012). Human ALKBH4 Interacts with Proteins Associated with Transcription. PLOS ONE. 7(11). doi: 10.1371/journal.pone.0049045. Full text in Research Archive Show summary

  The Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from E. coli is a demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct reversal mechanism. Humans possess nine AlkB homologs (ALKBH1-8 and FTO). ALKBH2 and ALKBH3 display demethylase activities corresponding to that of AlkB, and both ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the rest of the homologs are still unknown. To increase our knowledge on the functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to identify interaction partners of the two proteins. While no high-confidence hits were detected in the case of ALKBH7, several proteins associated with chromatin and/or involved in transcription were found to interact with ALKBH4. For all interaction partners, the regions mediating binding to ALKBH4 comprised domains previously reported to be involved in interaction with DNA or chromatin. Furthermore, some of these partners showed nuclear co-localization with ALKBH4. However, the global gene expression pattern was only marginally altered upon ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7. Although the molecular function of both proteins remains to be revealed, our findings suggest a role for ALKBH4 in regulation of gene expression or chromatin state.

• Korvald, Hanne; Falnes, Pål; Lærdahl, Jon Kristen; Bjørås, Magnar & Alseth, Ingrun (2012). The Schizosaccharomyces pombe AlkB homolog Abh1 exhibits AP lyase activity but no demethylase activity. DNA Repair. ISSN 1568-7864. 11(5), p. 453–462. doi: 10.1016/j.dnarep.2012.01.014. Full text in Research Archive
• Bjørnstad, Linn; Zoppellaro, Giorgio; Tomter, Ane Berg; Falnes, Pål & Andersson, K. Kristoffer (2011). Spectroscopic and Magnetic Studies of wild-type and mutant forms of the FeII and 2-oxoglutarate dependent decarboxylase ALKBH4. Biochemical Journal. ISSN 0264-6021. 434(3), p. 391–398. doi: 10.1042/BJ20101667. Full text in Research Archive Show summary

  The FeII/2-oxoglutarate (2OG)-dependent dioxygenase superfamily comprises proteins that couple a wide range of oxidation reactions to decarboxylation of 2-oxoglutarate to succinate. A member of this class of mononuclear non-heme iron proteins is the E. coli DNA/RNA repair enzyme AlkB. In this work, we describe the magnetic and optical properties of the yet uncharacterized human AlkB homologue ALKBH4. Through EPR and UV-Vis spectroscopy studies, we address the iron binding environment of the proposed catalytic centre of wild-type ALKBH4 and an FeII binding mutant. We could observe a novel unusal ferric high spin EPR active species in presence of sulfide with gmax 8.2. The FeII site was probed with NO. An intact histidine-carboxylate site is necessary for productive iron binding. We also report the presence of a unique cysteine-rich motif conserved in the N-terminus of ALKBH4 orthologues, and investigate its possible iron binding ability. Furthermore, we show that recombinant ALKBH4 mediates decarboxylation of 2-oxoglutarate in absence of primary substrate. This activity is dependent on iron as well as on residues predicted to be involved in FeII coordination. Our results demonstrate that ALKBH4 represent an active FeII/2OG-dependent decarboxylase, and suggest the cysteine cluster to be involved in other processes than iron coordination.

• Leihne, VIbeke; Kirpekar, F; Vågbø, Cathrine Broberg; Born, Erwin Van den; Krokan, Hans Einar & Grini, Paul Eivind [Show all 8 contributors for this article] (2011). Roles of Trm9-and ALKBH8-like proteins in the formation of modified wobble uridines in Arabidopsis tRNA. Nucleic Acids Research (NAR). ISSN 0305-1048. 39(17), p. 7688–7701. doi: 10.1093/nar/gkr406. Full text in Research Archive Show summary

  Uridine at the wobble position of tRNA is usually modified, and modification is required for accurate and efficient protein translation. In eukaryotes, wobble uridines are modified into 5-methoxycarbonylmethyluridine (mcm 5 U), 5-carbamoylmethyluridine (ncm 5 U) or derivatives thereof. Here, we demonstrate, both by in vitro and in vivo studies, that the Arabidopsis thaliana methyltransferase AT1G31600, denoted by us AtTRM9, is responsible for the final step in mcm 5 U formation, thus representing a functional homologue of the Saccharomyces cerevisiae Trm9 protein. We also show that the enzymatic activity of AtTRM9 depends on either one of two closely related proteins, AtTRM112a and AtTRM112b. Moreover, we demonstrate that AT1G36310, denoted AtALKBH8, is required for hydroxylation of mcm 5 U to ( S ) - mchm 5 U in tRNA GlyUCC , and has a function similar to the mammalian dioxygenase ALKBH8. Interestingly, atalkbh8 mutant plants displayed strongly increased levels of mcm 5 U, and also of mcm 5 Um, its 2′- O -ribose methylated derivative. This suggests that accumulated mcm 5 U is prone to further ribose methylation by a non-specialized mechanism, and may challenge the notion that the existence of mcm 5 U- and mcm 5 Um-containing forms of the selenocysteine-specific tRNA Sec in mammals reflects an important regulatory process. The present study reveals a role in for several hitherto uncharacterized Arabidopsis proteins in the formation of modified wobble uridines.

• Born, Erwin Van den; Vågbø, Cathrine Broberg; Songe-Møller, Lene; Leihne, VIbeke; Lien, Guro Flor & Leszczynska, G [Show all 11 contributors for this article] (2011). ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA. Nature Communications. 2. doi: 10.1038/ncomms1173. Full text in Research Archive Show summary

  Mammals have nine different homologues (ALKBH1–9) of the Escherichia coli DNA repair demethylase AlkB. ALKBH2 is a genuine DNA repair enzyme, but the in vivo function of the other ALKBH proteins has remained elusive. It was recently shown that ALKBH8 contains an additional transfer RNA (tRNA) methyltransferase domain, which generates the wobble nucleoside 5-methoxycarbonylmethyluridine (mcm5U) from its precursor 5-carboxymethyluridine (cm5U). In this study, we report that (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm5U), hydroxylated forms of mcm5U, are present in mammalian , and , respectively, representing the first example of a diastereomeric pair of modified RNA nucleosides. Through in vitro and in vivo studies, we show that both diastereomers of mchm5U are generated from mcm5U, and that the AlkB domain of ALKBH8 specifically hydroxylates mcm5U into (S)-mchm5U in . These findings expand the function of the ALKBH oxygenases beyond nucleic acid repair and increase the current knowledge on mammalian wobble uridine modifications and their biogenesis.

• Songe-Møller, Lene; Born, Erwin Van den; Leihne, V; Vågbø, Cathrine Broberg; Kristoffersen, T & Krokan, Hans Einar [Show all 9 contributors for this article] (2010). Mammalian ALKBH8 Possesses tRNA Methyltransferase Activity Required for the Biogenesis of Multiple Wobble Uridine Modifications Implicated in Translational Decoding. Molecular and Cellular Biology. ISSN 0270-7306. 30(7), p. 1814–1827. doi: 10.1128/MCB.01602-09. Full text in Research Archive
• Falnes, Pål; Born, Erwin Van den & Meza, Trine Johansen (2009). Demethylation of DNA and RNA by AlkB proteins. In Grosjean, Henri (Eds.), DNA and RNA modification enzymes. Landes Bioscience. ISSN 9781587063299. p. 170–180. Full text in Research Archive
• Born, Erwin Van den; Bekkelund, Anders; Moen, Marivi; Omelchenko, M.V.; Klungland, Arne & Falnes, Pål (2009). Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria. Nucleic Acids Research (NAR). ISSN 0305-1048. 37(21). doi: 10.1093/nar/gkp774. Full text in Research Archive
• Born, Erwin Van den; Omelchenko, M.V.; Bekkelund, Anders; Leihne, VIbeke; Koonin, E. V. & Dolja, V.V. [Show all 7 contributors for this article] (2008). Viral AlkB proteins repair RNA damage by oxidative demethylation. Nucleic Acids Research (NAR). ISSN 0305-1048. 36(17), p. 5451–5461. doi: 10.1093/nar/gkn519. Full text in Research Archive
• Wærsted, Jeanette Ringvoll; Nabong, Marivi; Nordstrand, Line Mari; Meira, LB; Pang, B & Bekkelund, Anders [Show all 11 contributors for this article] (2008). AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Research. ISSN 0008-5472. 68(11), p. 4142–4149. doi: 10.1158/0008-5472.CAN-08-0796. Full text in Research Archive Show summary

  Endogenous formation of the mutagenic DNA adduct 1,N6-ethenoadenine ({varepsilon}A) originates from lipid peroxidation. Elevated levels of {varepsilon}A in cancer-prone tissues suggest a role for this adduct in the development of some cancers. The base excision repair pathway has been considered the principal repair system for {varepsilon}A lesions until recently, when it was shown that the Escherichia coli AlkB dioxygenase could directly reverse the damage. We report here kinetic analysis of the recombinant human AlkB homologue 2 (hABH2), which is able to repair {varepsilon}A lesions in DNA. Furthermore, cation exchange chromatography of nuclear extracts from wild-type and mABH2–/– mice indicates that mABH2 is the principal dioxygenase for {varepsilon}A repair in vivo. This is further substantiated by experiments showing that hABH2, but not hABH3, is able to complement the E. coli alkB mutant with respect to its defective repair of etheno adducts. We conclude that ABH2 is active in the direct reversal of {varepsilon}A lesions, and that ABH2, together with the alkyl-N-adenine-DNA glycosylase, which is the most effective enzyme for the repair of {varepsilon}A, comprise the cellular defense against {varepsilon}A lesions. [Cancer Res 2008;68(11):4142–9]

• Ringvoll, Jeanette; Moen, Marivi N.; Nordstrand, Line M.; Meira, Lisiane B.; Pang, Bo & Bekkelund, Anders [Show all 11 contributors for this article] (2008). AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Research. ISSN 0008-5472. 68(11), p. 4142–4149. Full text in Research Archive Show summary

  Endogenous formation of the mutagenic DNA adduct 1,N-6-ethenoadenine (epsilon A) originates from lipid peroxidation. Elevated levels of epsilon A in cancer-prone tissues suggest a role for this adduct in the development of some cancers. The base excision repair pathway has been considered the principal repair system for epsilon A lesions until recently, when it was shown that the Escherichia coli AlkB dioxygenase could directly reverse the damage. We report here kinetic analysis of the recombinant human AlkB homologue 2 (hABH2), which is able to repair epsilon A lesions in DNA. Furthermore, cation exchange chromatography of nuclear extracts from wild-type and mABH2(-/-) mice indicates that mABH2 is the principal dioxygenase for EA repair in vivo. This is further substantiated by experiments showing that hABH2, but not hABH3, is able to complement the E. coli alkB mutant with respect to its defective repair of etheno adducts. We conclude that ABH2 is active in the direct reversal of epsilon A lesions, and that ABH2, together with the alkyl-N-adenine-DNA glycosylase, which is the most effective enzyme for the repair of epsilon A, comprise the cellular defense against epsilon A lesions.

• Falnes, Pål; Klungland, Arne & Alseth, Ingrun (2007). Repair of methyl lesions in DNA and RNA by oxidative demethylation. Neuroscience. ISSN 0306-4522. 145. doi: 10.1016/j.neuroscience.2006.11.018. Full text in Research Archive
• Ringvoll, Jeanette; Ringvoll, Jeanette; Nordstrand, Line M.; Vågbø, Cathrine Broberg; Vagbo, CB & Talstad, Vivi [Show all 15 contributors for this article] (2006). Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA. EMBO Journal. ISSN 0261-4189. 25, p. 2189–2198. Full text in Research Archive
• Falnes, Pål (2005). RNA repair - the latest addition to the toolbox for macromolecular maintenance. RNA Biology. ISSN 1547-6286. 2(1), p. 14–16. Full text in Research Archive
• Aamodt, Randi; Falnes, Pål; Johansen, RF; Seeberg, Erling Christen & Bjørås, Magnar (2004). The Bacillus subtilis counterpart of the mammalian 3-methyladenine DNA glycosylase has hypoxanthine and 1,N-6-ethenoadenine as preferred substrates. Journal of Biological Chemistry. ISSN 0021-9258. 279, p. 13601–13606. Full text in Research Archive
• Falnes, Pål (2004). Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins. Nucleic Acids Research (NAR). ISSN 0305-1048. 32(21), p. 6260–6267. Full text in Research Archive
• Ougland, Rune; Zhang, Chun-mei; Liiv, Aivar; Johansen, Rune F.; Seeberg, Erling Christen & Hou, Ya-ming [Show all 8 contributors for this article] (2004). AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Molecular Cell. ISSN 1097-2765. 16(1), p. 107–116. Full text in Research Archive
• Falnes, Pål; Bjoras, M; Bjørås, Magnar; Aas, PA; Sundheim, Ottar & Seeberg, E (2004). Substrate specificities of bacterial and human AlkB proteins. Nucleic Acids Research (NAR). ISSN 0305-1048. 30(11), p. 3456–3461. Full text in Research Archive

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• Falnes, Pål (2024). The versatile seven-beta-strand methyltransferase family. Full text in Research Archive
• Falnes, Pål (2024). A tour of the landscape of human seven-β-strand methyltransferases. Full text in Research Archive
• Falnes, Pål (2023). Unravelling novel methyltransferases involved in protein and nucleic acid methylation. Full text in Research Archive
• Falnes, Pål (2022). Discovering novel lysine-specific protein methyltransferases. Full text in Research Archive
• Falnes, Pål (2022). Discovering novel human histidine methyltransferases. Full text in Research Archive
• Falnes, Pål (2022). Using mass spectrometry to study methylation of nucleic acids and proteins. Full text in Research Archive
• Falnes, Pål Øystein (2020). Novel human methyltransferases - roles in mitochondrial respiration, protein synthesis and beyond. Full text in Research Archive
• Falnes, Pål Øystein (2019). Regulation of protein synthesis through methylation of human eukaryotic elongation factor 1 alpha (eEF1A). Full text in Research Archive
• Falnes, Pål Øystein (2019). Modulation of human mitochondrial metabolism by novel lysine-specific methyltransferases. Full text in Research Archive
• Falnes, Pål Øystein (2019). Identification and characterisation of novel human methyltransferases. Full text in Research Archive
• Falnes, Pål Øystein (2019). "Nobelprisen i kjemi 2018" (om dirigert evolusjon). Full text in Research Archive
• Falnes, Pål Øystein (2018). Regulation of human eukaryotic elongation factor 1 alpha (eEF1A) by lysine methylation. Full text in Research Archive
• Falnes, Pål Øystein (2018). Discovering new human enzymes involved in methylation and demethylation of nucleic acids and proteins. Full text in Research Archive
• Falnes, Pål (2017). Identification and characterisation of lysine-specific methyltransferases in humans. Full text in Research Archive
• Falnes, Pål (2016). Metylering av DNA og proteiner - både skadelig og nødvendig. Full text in Research Archive
• Aileni, Vinay Kumar; Davydova, Erna; Kernstock, Jens Stefan; Moen, Anders & Falnes, Pål (2016). VCP-KMT (METTL21D)-mediated lysine methylation of histone H3 peptide sequences grafted onto a VCP-derived scaffold. Full text in Research Archive
• Jakobsson, Magnus; Moen, Anders; Davidson, Ben & Falnes, Pål (2016). METTL21A-catalysed lysine methylation of Hsp70 proteins. Full text in Research Archive
• Falnes, Pål (2016). Lysine methylation of non-histone proteins - new enzymes, new functions. Full text in Research Archive
• Jakobsson, Magnus; Moen, Anders & Falnes, Pål (2016). Correspondence: On the enzymology and significance of HSPA1 lysine methylation. Nature Communications. 7. doi: 10.1038/ncomms11464. Full text in Research Archive
• Falnes, Pål (2015). Discovering new human enzymes involved in methylation and demethylation of nucleic acids and proteins. Full text in Research Archive
• Falnes, Pål (2015). Discovering new human enzymes involved in methylation and demethylation of nucleic acids and proteins. Full text in Research Archive
• Falnes, Pål (2015). Metylering av DNA og proteiner– skadelig og nødvendig. Full text in Research Archive
• Falnes, Pål (2015). Merkelapper på DNA og proteiner – både skadelig og nødvendig. Full text in Research Archive
• Falnes, Pål & Ho, Angela Yeuan Yen (2015). Role of ALKBH8 in the Synthesis of Wobble Uridine Modifications in tRNA. In Schofield, Christopher J. & Hausinger, Robert (Ed.), 2-Oxoglutarate-Dependent Oxygenases. Royal Society of Chemistry (RSC). ISSN 9781849739504. p. 275–288. doi: 10.1039/9781782621959-00275. Full text in Research Archive
• Falnes, Pål (2014). Functional characterization of a novel family of protein lysine methyltransferases. Full text in Research Archive
• Falnes, Pål (2014). Discovering new human enzymes involved in methylation and demethylation of nucleic acids and proteins. Full text in Research Archive
• Falnes, Pål (2013). Role of the bifunctional ALKBH8 enzyme in the formation of modified wobble uridines in tRNA. Full text in Research Archive
• Falnes, Pål (2012). Merkelapper på DNA og proteiner – både skadelig og nødvendig. Full text in Research Archive
• Falnes, Pål (2012). Merkelapper på DNA og proteiner –både skadelig og nødvendig. Full text in Research Archive
• Bjørnstad, Linn; Zoppellaro, Giorgio; Tomter, Ane Berg; Falnes, Pål & Andersson, K. Kristoffer (2011). Spectroscopic and Magnetic Studies of wild-type and mutant forms of the FeII and 2-oxoglutarate dependent decarboxylase ALKBH4. Full text in Research Archive
• Meza, Trine Johansen; Moen, Marivi N.; Vågbø, Cathrine B.; Ulleland, Marius; Krokan, Hans Einar & Arne, Klungland [Show all 8 contributors for this article] (2010). The DNA dioxygenase AtALKBH2 protects Arabidopsis thaliana against methylation damage. Full text in Research Archive
• Falnes, Pål (2009). AlkB-like dioxygenases - roles in nucleic acid repair and modification. Full text in Research Archive
• Falnes, Pål (2009). Oxidative demethylation of RNA by AlkB proteins. Full text in Research Archive
• Falnes, Pål; Born, Erwin Van den; Leihne, VIbeke; Meza, Trine Johansen; Songe-Møller, Lene & Klungland, Arne (2009). AlkB-like dioxygenases-roles in nucleic acid repair and modification. Full text in Research Archive
• Falnes, Pål (2008). "DNA and RNA repair by AlkB-mediated oxidative demethylation". Full text in Research Archive
• Falnes, Pål (2008). RNA repair by oxidative demethylation. Full text in Research Archive
• Falnes, Pål (2007). Oxidative demethylation of DNA, RNA, and proteins by AlkB-like enzymes. Full text in Research Archive
• Falnes, Pål (2007). DNA and RNA repair by human and bacterial AlkB proteins. Full text in Research Archive
• Falnes, Pål (2006). A novel mechanism for demethylation of DNA, RNA, and proteins. Full text in Research Archive
• Falnes, Pål; Ougland, Rune; Bekkelund, Anders & Ulleland, Marius Andreas (2006). DNA and RNA repair by human and bacterial ALkB proteins. Full text in Research Archive
• Falnes, Pål (2006). Repair of methyl lesions in DNA and RNA by oxidative demetylation. Full text in Research Archive
• Ougland, Rune; Zhang, Chun-mei; Liiv, Aivar; Johansen, Rune F.; Seeberg, Erling & Hou, Ya-ming [Show all 8 contributors for this article] (2005). Functional recovery of chemically methylated mRNA and tRNA by AlkB-mediated repair. Full text in Research Archive
• Falnes, Pål (2005). AlkB proteins – in general and in Arabidopsis. Full text in Research Archive
• Ougland, Rune; Zhang, Chun-mei; Liiv, Aivar; Johansen, Rune F.; Seeberg, Erling Christen & Remme, Jaanus [Show all 8 contributors for this article] (2004). AlkB mediated repair of methyl lesions in mRNA and tRNA is accompanied by functional recovery. Full text in Research Archive
• Falnes, Pål (2004). Repair of alkylation damage in DNA and RNA. Full text in Research Archive
• Falnes, Pål (2004). Recovery of RNA function upon AlkB mediated repair of alkyl lesions. Full text in Research Archive
• Falnes, Pål; Johansen, Rune F. & Seeberg, Erling Christen (2003). A third mechanism for DNA damage reversal catalysed by AlkB protein in E. coli. Full text in Research Archive
• Naseri, Nafasgol; Dahal-Koirala, Shiva; Haapaniemi, Emma Maria & Falnes, Pål (2026). Investigation of on-target Chromosomal deletions and loss during HDR-enhanced CRISPR-Cas9 correction of a CARMIL2 point mutation in patient-derived T cells. University of Oslo (UiO). Full text in Research Archive
• Borg, Nora Helene Hammersten; Komisarczuk, Anna Zofia; Falnes, Pål & Haapaniemi, Emma Maria (2026). Development of a Multimodal Screening Platform for Comparative Evaluation of Prime Editing Efficiency. Establishing an experimental framework through reporter cell line generation, prime editing vector construction, and detection assay development. Universitetet i Oslo. Full text in Research Archive Show summary

  --- Abstract will be published: 2027-05-19

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