1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Biochemistry
  4. Volume 93, 2024
  5. Article

Annual Review of Biochemistry

Volume 93, 2024

How Natural Enzymes and Synthetic Ribozymes Generate Methylated Nucleotides in RNA

Abstract

Methylation of RNA nucleotides represents an important layer of gene expression regulation, and perturbation of the RNA methylome is associated with pathophysiology. In cells, RNA methylations are installed by RNA methyltransferases (RNMTs) that are specialized to catalyze particular types of methylation (ribose or different base positions). Furthermore, RNMTs must specifically recognize their appropriate target RNAs within the RNA-dense cellular environment. Some RNMTs are catalytically active alone and achieve target specificity via recognition of sequence motifs and/or RNA structures. Others function together with protein cofactors that can influence stability, -adenosyl-L-methionine binding, and RNA affinity as well as aiding specific recruitment and catalytic activity. Association of RNMTs with guide RNAs represents an alternative mechanism to direct site-specific methylation by an RNMT that lacks intrinsic specificity. Recently, ribozyme-catalyzed methylation of RNA has been achieved in vitro, and here, we compare these different strategies for RNA methylation from structural and mechanistic perspectives.

Keyword(s): epitranscriptome, methyltransferase, ribozyme, RNA modification, Rossmann fold, small nucleolar RNP
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-030222-112310
2024-08-02
2025-04-24
Loading full text...

Full text loading...

/deliver/fulltext/biochem/93/1/annurev-biochem-030222-112310.html?itemId=/content/journals/10.1146/annurev-biochem-030222-112310&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Roundtree IA, Evans ME, Pan T, He C. 2017.. Dynamic RNA modifications in gene expression regulation. . Cell 169:(7):1187–200
     [Crossref] [Google Scholar]
  2. 2.
    Sloan KE, Warda AS, Sharma S, Entian K-D, Lafontaine DLJ, Bohnsack MT. 2017.. Tuning the ribosome: the influence of rRNA modification on eukaryotic ribosome biogenesis and function. . RNA Biol. 14:(9):1138–52
     [Crossref] [Google Scholar]
  3. 3.
    Bohnsack MT, Sloan KE. 2018.. Modifications in small nuclear RNAs and their roles in spliceosome assembly and function. . Biol. Chem. 399:(11):1265–76
     [Crossref] [Google Scholar]
  4. 4.
    Suzuki T. 2021.. The expanding world of tRNA modifications and their disease relevance. . Nat. Rev. Mol. Cell Biol. 22:(6):375–92
     [Crossref] [Google Scholar]
  5. 5.
    Gilbert WV, Nachtergaele S. 2023.. mRNA regulation by RNA modifications. . Annu. Rev. Biochem. 92::175–98
     [Crossref] [Google Scholar]
  6. 6.
    Motorin Y, Helm M. 2022.. RNA nucleotide methylation: 2021 update. . WIREs RNA 13:(1):e1691
     [Crossref] [Google Scholar]
  7. 7.
    Ontiveros RJ, Stoute J, Liu KF. 2019.. The chemical diversity of RNA modifications. . Biochem. J. 476:(8):1227–45
     [Crossref] [Google Scholar]
  8. 8.
    Helm M, Motorin Y. 2017.. Detecting RNA modifications in the epitranscriptome: predict and validate. . Nat. Rev. Genet. 18:(5):275–91
     [Crossref] [Google Scholar]
  9. 9.
    Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B, et al. 2018.. MODOMICS: a database of RNA modification pathways. 2017 update. . Nucleic Acids Res. 46:(D1):D303–7
     [Crossref] [Google Scholar]
  10. 10.
    Petrossian TC, Clarke SG. 2011.. Uncovering the human methyltransferasome. . Mol. Cell Proteom. 10:(1):M110.000976
     [Crossref] [Google Scholar]
  11. 11.
    Graille M. 2022.. Division of labor in epitranscriptomics: What have we learnt from the structures of eukaryotic and viral multimeric RNA methyltransferases?. WIREs RNA 13:(1):e1673
     [Crossref] [Google Scholar]
  12. 12.
    Frye M, Harada BT, Behm M, He C. 2018.. RNA modifications modulate gene expression during development. . Science 361:(6409):1346–49
     [Crossref] [Google Scholar]
  13. 13.
    Boo SH, Kim YK. 2020.. The emerging role of RNA modifications in the regulation of mRNA stability. . Exp. Mol. Med. 52:(3):400–8
     [Crossref] [Google Scholar]
  14. 14.
    Fenwick MK, Ealick SE. 2018.. Towards the structural characterization of the human methyltransferome. . Curr. Opin. Struct. Biol. 53::12–21
     [Crossref] [Google Scholar]
  15. 15.
    Fischer TR, Meidner L, Schwickert M, Weber M, Zimmermann RA, et al. 2022.. Chemical biology and medicinal chemistry of RNA methyltransferases. . Nucleic Acids Res. 50:(8):4216–45
     [Crossref] [Google Scholar]
  16. 16.
    Schrödinger LLC. 2015.. The PyMOL molecular graphics system, version 2.3.1. . Molecular Visualization Software. https://pymol.org/
    [Google Scholar]
  17. 17.
    Rossmann MG, Moras D, Olsen KW. 1974.. Chemical and biological evolution of nucleotide-binding protein. . Nature 250:(463):194–99
     [Crossref] [Google Scholar]
  18. 18.
    Chouhan BPS, Maimaiti S, Gade M, Laurino P. 2019.. Rossmann-fold methyltransferases: taking a “β-turn” around their cofactor, S-adenosylmethionine. . Biochemistry 58:(3):166–70
     [Crossref] [Google Scholar]
  19. 19.
    Oerum S, Meynier V, Catala M, Tisné C. 2021.. A comprehensive review of m6A/m6Am RNA methyltransferase structures. . Nucleic Acids Res. 49:(13):7239–55
     [Crossref] [Google Scholar]
  20. 20.
    Wang C, Ulryck N, Herzel L, Pythoud N, Kleiber N, et al. 2023.. N2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing. . Nucleic Acids Res. 51:(14):gkad487
     [Google Scholar]
  21. 21.
    Bujnicki JM. 2002.. Sequence permutations in the molecular evolution of DNA methyltransferases. . BMC Evol. Biol. 2::3
     [Crossref] [Google Scholar]
  22. 22.
    Tkaczuk KL, Dunin-Horkawicz S, Purta E, Bujnicki JM. 2007.. Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases. . BMC Bioinform. 8::73
     [Crossref] [Google Scholar]
  23. 23.
    Taylor AB, Meyer B, Leal BZ, Kötter P, Schirf V, et al. 2008.. The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site. . Nucleic Acids Res. 36:(5):1542–54
     [Crossref] [Google Scholar]
  24. 24.
    Krishnamohan A, Jackman JE. 2019.. A family divided: distinct structural and mechanistic features of the SpoU-TrmD (SPOUT) methyltransferase superfamily. . Biochemistry 58:(5):336–45
     [Crossref] [Google Scholar]
  25. 25.
    Yan F, Fujimori DG. 2011.. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. . PNAS 108:(10):3930–34
     [Crossref] [Google Scholar]
  26. 26.
    Tsai K, Stojković V, Noda-Garcia L, Young ID, Myasnikov AG, et al. 2022.. Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance. . eLife 11::e70017
     [Crossref] [Google Scholar]
  27. 27.
    Fujimori DG. 2013.. Radical SAM-mediated methylation reactions. . Curr. Opin. Chem. Biol. 17:(4):597–604
     [Crossref] [Google Scholar]
  28. 28.
    Hamdane D, Grosjean H, Fontecave M. 2016.. Flavin-dependent methylation of RNAs: complex chemistry for a simple modification. . J. Mol. Biol. 428:(24 Part B):4867–81
     [Crossref] [Google Scholar]
  29. 29.
    Bohnsack KE, Höbartner C, Bohnsack MT. 2019.. Eukaryotic 5-methylcytosine (m5C) RNA methyltransferases: mechanisms, cellular functions, and links to disease. . Genes 10:(2):102
     [Crossref] [Google Scholar]
  30. 30.
    Liao H, Gaur A, McConie H, Shekar A, Wang K, et al. 2022.. Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs. . Nucleic Acids Res. 50:(18):10695–716
     [Crossref] [Google Scholar]
  31. 31.
    Haag S, Sloan KE, Ranjan N, Warda AS, Kretschmer J, et al. 2016.. NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation. . EMBO J. 35:(19):2104–19
     [Crossref] [Google Scholar]
  32. 32.
    Nakano S, Suzuki T, Kawarada L, Iwata H, Asano K, Suzuki T. 2016.. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNAMet. . Nat. Chem. Biol. 12:(7):546–51
     [Crossref] [Google Scholar]
  33. 33.
    Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, et al. 2016.. Deficient methylation and formylation of mt-tRNAMet wobble cytosine in a patient carrying mutations in NSUN3. . Nat. Commun. 7::12039
     [Crossref] [Google Scholar]
  34. 34.
    Metodiev MD, Spåhr H, Loguercio Polosa P, Meharg C, Becker C, et al. 2014.. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. . PLOS Genet. 10:(2):e1004110
     [Crossref] [Google Scholar]
  35. 35.
    Janin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P, et al. 2019.. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. . Acta Neuropathol. 138:(6):1053–74
     [Crossref] [Google Scholar]
  36. 36.
    Aguilo F, Li S, Balasubramaniyan N, Sancho A, Benko S, et al. 2016.. Deposition of 5-methylcytosine on enhancer RNAs enables the coactivator function of PGC-1α. . Cell Rep. 14:(3):479–92
     [Crossref] [Google Scholar]
  37. 37.
    Selmi T, Hussain S, Dietmann S, Heiß M, Borland K, et al. 2021.. Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6. . Nucleic Acids Res. 49:(2):1006–22
     [Crossref] [Google Scholar]
  38. 38.
    Haag S, Warda AS, Kretschmer J, Günnigmann MA, Höbartner C, Bohnsack MT. 2015.. NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. . RNA 21:(9):1532–43
     [Crossref] [Google Scholar]
  39. 39.
    Shinoda S, Kitagawa S, Nakagawa S, Wei F-Y, Tomizawa K, et al. 2019.. Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs. . Nucleic Acids Res. 47:(16):8734–45
     [Crossref] [Google Scholar]
  40. 40.
    Van Haute L, Lee S-Y, McCann BJ, Powell CA, Bansal D, et al. 2019.. NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs. . Nucleic Acids Res. 47:(16):8720–33
     [Crossref] [Google Scholar]
  41. 41.
    Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, et al. 2014.. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. . EMBO J. 33:(18):2020–39
     [Crossref] [Google Scholar]
  42. 42.
    Hussain S, Sajini AA, Blanco S, Dietmann S, Lombard P, et al. 2013.. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. . Cell Rep. 4:(2):255–61
     [Crossref] [Google Scholar]
  43. 43.
    Liu R-J, Long T, Li J, Li H, Wang E-D. 2017.. Structural basis for substrate binding and catalytic mechanism of a human RNA:m5C methyltransferase NSun6. . Nucleic Acids Res. 45:(11):6684–97
     [Crossref] [Google Scholar]
  44. 44.
    Bohnsack KE, Kleiber N, Lemus-Diaz N, Bohnsack MT. 2022.. Roles and dynamics of 3-methylcytidine in cellular RNAs. . Trends Biochem. Sci. 47:(7):596–608
     [Crossref] [Google Scholar]
  45. 45.
    Xu L, Liu X, Sheng N, Oo KS, Liang J, et al. 2017.. Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and mRNA in mice and humans. . J. Biol. Chem. 292:(35):14695–703
     [Crossref] [Google Scholar]
  46. 46.
    Kleiber N, Lemus-Diaz N, Stiller C, Heinrichs M, Mai MM-Q, et al. 2022.. The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation. . Nat. Commun. 13:(1):209
     [Crossref] [Google Scholar]
  47. 47.
    Schöller E, Marks J, Marchand V, Bruckmann A, Powell CA, et al. 2021.. Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs. . Mol. Cell 81:(23):4810–25.e12
     [Crossref] [Google Scholar]
  48. 48.
    Mao X-L, Li Z-H, Huang M-H, Wang J-T, Zhou J-B, et al. 2021.. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. . Nucleic Acids Res. 49:(14):8309–23
     [Crossref] [Google Scholar]
  49. 49.
    Ignatova VV, Kaiser S, Ho JSY, Bing X, Stolz P, et al. 2020.. METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth. . Sci. Adv. 6:(35):eaaz4551
     [Crossref] [Google Scholar]
  50. 50.
    D'Silva S, Haider SJ, Phizicky EM. 2011.. A domain of the actin binding protein Abp140 is the yeast methyltransferase responsible for 3-methylcytidine modification in the tRNA anti-codon loop. . RNA 17:(6):1100–10
     [Crossref] [Google Scholar]
  51. 51.
    Han L, Marcus E, D'Silva S, Phizicky EM. 2017.. S. cerevisiae Trm140 has two recognition modes for 3-methylcytidine modification of the anticodon loop of tRNA substrates. . RNA 23:(3):406–19
     [Crossref] [Google Scholar]
  52. 52.
    Noma A, Yi S, Katoh T, Takai Y, Suzuki T, Suzuki T. 2011.. Actin-binding protein ABP140 is a methyltransferase for 3-methylcytidine at position 32 of tRNAs in Saccharomyces cerevisiae. . RNA 17:(6):1111–19
     [Crossref] [Google Scholar]
  53. 53.
    Li S, Zhou H, Liao S, Wang X, Zhu Z, et al. 2022.. Structural basis for METTL6-mediated m3C RNA methylation. . Biochem. Biophys. Res. Commun. 589::159–64
     [Crossref] [Google Scholar]
  54. 54.
    Chen R, Zhou J, Liu L, Mao X-L, Zhou X, Xie W. 2021.. Crystal structure of human METTL6, the m3C methyltransferase. . Commun. Biol. 4:(1):1361
     [Crossref] [Google Scholar]
  55. 55.
    Ignatova VV, Jansen PWTC, Baltissen MP, Vermeulen M, Schneider R. 2019.. The interactome of a family of potential methyltransferases in HeLa cells. . Sci. Rep. 9:(1):6584
     [Crossref] [Google Scholar]
  56. 56.
    van Tran N, Ernst FGM, Hawley BR, Zorbas C, Ulryck N, et al. 2019.. The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. . Nucleic Acids Res. 47:(15):7719–33
     [Crossref] [Google Scholar]
  57. 57.
    Ma H, Wang X, Cai J, Dai Q, Natchiar SK, et al. 2019.. N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation. . Nat. Chem. Biol. 15:(1):88–94
     [Crossref] [Google Scholar]
  58. 58.
    Chen H, Gu L, Orellana EA, Wang Y, Guo J, et al. 2020.. METTL4 is an snRNA m6Am methyltransferase that regulates RNA splicing. . Cell Res. 30:(6):544–47
     [Crossref] [Google Scholar]
  59. 59.
    Goh YT, Koh CWQ, Sim DY, Roca X, Goh WSS. 2020.. METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing. . Nucleic Acids Res. 48:(16):9250–61
     [Crossref] [Google Scholar]
  60. 60.
    Pendleton KE, Chen B, Liu K, Hunter OV, Xie Y, et al. 2017.. The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. . Cell 169:(5):824–35.e14
     [Crossref] [Google Scholar]
  61. 61.
    Warda AS, Kretschmer J, Hackert P, Lenz C, Urlaub H, et al. 2017.. Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. . EMBO Rep. 18:(11):2004–14
     [Crossref] [Google Scholar]
  62. 62.
    Akichika S, Hirano S, Shichino Y, Suzuki T, Nishimasu H, et al. 2019.. Cap-specific terminal N6-methylation of RNA by an RNA polymerase II–associated methyltransferase. . Science 363:(6423):eaav0080
     [Crossref] [Google Scholar]
  63. 63.
    Luo Q, Mo J, Chen H, Hu Z, Wang B, et al. 2022.. Structural insights into molecular mechanism for N6-adenosine methylation by MT-A70 family methyltransferase METTL4. . Nat. Commun. 13:(1):5636
     [Crossref] [Google Scholar]
  64. 64.
    Doxtader KA, Wang P, Scarborough AM, Seo D, Conrad NK, Nam Y. 2018.. Structural basis for regulation of METTL16, an S-adenosylmethionine homeostasis factor. . Mol. Cell 71:(6):1001–11.e4
     [Crossref] [Google Scholar]
  65. 65.
    Ren W, Lu J, Huang M, Gao L, Li D, et al. 2019.. Structure and regulation of ZCCHC4 in m6A-methylation of 28S rRNA. . Nat. Commun. 10:(1):5042
     [Crossref] [Google Scholar]
  66. 66.
    Aoyama T, Yamashita S, Tomita K. 2020.. Mechanistic insights into m6A modification of U6 snRNA by human METTL16. . Nucleic Acids Res. 48:(9):5157–68
     [Crossref] [Google Scholar]
  67. 67.
    Sendinc E, Valle-Garcia D, Dhall A, Chen H, Henriques T, et al. 2019.. PCIF1 catalyzes m6Am mRNA methylation to regulate gene expression. . Mol. Cell 75:(3):620–30.e9
     [Crossref] [Google Scholar]
  68. 68.
    Sun H, Zhang M, Li K, Bai D, Yi C. 2019.. Cap-specific, terminal N6-methylation by a mammalian m6Am methyltransferase. . Cell Res. 29:(1):80–82
     [Crossref] [Google Scholar]
  69. 69.
    Meyer B, Wurm JP, Kötter P, Leisegang MS, Schilling V, et al. 2011.. The Bowen–Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Ψ1191 in yeast 18S rRNA. . Nucleic Acids Res. 39:(4):1526–37
     [Crossref] [Google Scholar]
  70. 70.
    Warda AS, Freytag B, Haag S, Sloan KE, Görlich D, Bohnsack MT. 2016.. Effects of the Bowen–Conradi syndrome mutation in EMG1 on its nuclear import, stability and nucleolar recruitment. . Hum. Mol. Genet. 25:(24):5353–64
     [Google Scholar]
  71. 71.
    Meyer B, Wurm JP, Sharma S, Immer C, Pogoryelov D, et al. 2016.. Ribosome biogenesis factor Tsr3 is the aminocarboxypropyl transferase responsible for 18S rRNA hypermodification in yeast and humans. . Nucleic Acids Res. 44:(9):4304–16
     [Crossref] [Google Scholar]
  72. 72.
    Wurm JP, Meyer B, Bahr U, Held M, Frolow O, et al. 2010.. The ribosome assembly factor Nep1 responsible for Bowen–Conradi syndrome is a pseudouridine-N1-specific methyltransferase. . Nucleic Acids Res. 38:(7):2387–98
     [Crossref] [Google Scholar]
  73. 73.
    Thomas SR, Keller CA, Szyk A, Cannon JR, LaRonde-LeBlanc NA. 2011.. Structural insight into the functional mechanism of Nep1/Emg1 N1-specific pseudouridine methyltransferase in ribosome biogenesis. . Nucleic Acids Res. 39:(6):2445–57
     [Crossref] [Google Scholar]
  74. 74.
    Kimura S, Miyauchi K, Ikeuchi Y, Thiaville PC, de Crécy-Lagard V, Suzuki T. 2014.. Discovery of the β-barrel-type RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs. . Nucleic Acids Res. 42:(14):9350–65
     [Crossref] [Google Scholar]
  75. 75.
    Ahn HJ, Kim H-W, Yoon H-J, Lee BI, Suh SW, Yang JK. 2003.. Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition. . EMBO J. 22:(11):2593–603
     [Crossref] [Google Scholar]
  76. 76.
    Nureki O, Watanabe K, Fukai S, Ishii R, Endo Y, et al. 2004.. Deep knot structure for construction of active site and cofactor binding site of tRNA modification enzyme. . Structure 12:(4):593–602
     [Crossref] [Google Scholar]
  77. 77.
    Bar-Yaacov D, Frumkin I, Yashiro Y, Chujo T, Ishigami Y, et al. 2016.. Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates. . PLOS Biol. 14:(9):e1002557
     [Crossref] [Google Scholar]
  78. 78.
    Chujo T, Suzuki T. 2012.. Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs. . RNA 18:(12):2269–76
     [Crossref] [Google Scholar]
  79. 79.
    Safra M, Sas-Chen A, Nir R, Winkler R, Nachshon A, et al. 2017.. The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. . Nature 551:(7679):251–55
     [Crossref] [Google Scholar]
  80. 80.
    Anderson J, Phan L, Hinnebusch AG. 2000.. The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae. . PNAS 97:(10):5173–78
     [Crossref] [Google Scholar]
  81. 81.
    Ozanick S, Krecic A, Andersland J, Anderson JT. 2005.. The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans. . RNA 11:(8):1281–90
     [Crossref] [Google Scholar]
  82. 82.
    Wang M, Zhu Y, Wang C, Fan X, Jiang X, et al. 2016.. Crystal structure of the two-subunit tRNA m1A58 methyltransferase TRM6-TRM61 from Saccharomyces cerevisiae. . Sci. Rep. 6:(1):32562
     [Crossref] [Google Scholar]
  83. 83.
    Finer-Moore J, Czudnochowski N, O'Connell JD, Wang AL, Stroud RM. 2015.. Crystal structure of the human tRNA m1A58 methyltransferase–tRNA3Lys complex: Refolding of substrate tRNA allows access to the methylation target. . J. Mol. Biol. 427:(24):3862–76
     [Crossref] [Google Scholar]
  84. 84.
    Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, et al. 2012.. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. . Nature 485:(7397):201–6
     [Crossref] [Google Scholar]
  85. 85.
    Liu J, Yue Y, Han D, Wang X, Fu Y, et al. 2014.. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. . Nat. Chem. Biol. 10:(2):93–95
     [Crossref] [Google Scholar]
  86. 86.
    Śledź P, Jinek M. 2016.. Structural insights into the molecular mechanism of the m6A writer complex. . eLife 5::e18434
     [Crossref] [Google Scholar]
  87. 87.
    Wang X, Feng J, Xue Y, Guan Z, Zhang D, et al. 2016.. Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex. . Nature 534:(7608):575–78
     [Crossref] [Google Scholar]
  88. 88.
    Schöller E, Weichmann F, Treiber T, Ringle S, Treiber N, et al. 2018.. Interactions, localization, and phosphorylation of the m6A generating METTL3–METTL14–WTAP complex. . RNA 24:(4):499–512
     [Crossref] [Google Scholar]
  89. 89.
    Su S, Li S, Deng T, Gao M, Yin Y, et al. 2022.. Cryo-EM structures of human m6A writer complexes. . Cell Res. 32:(11):982–94
     [Crossref] [Google Scholar]
  90. 90.
    Ping X-L, Sun B-F, Wang L, Xiao W, Yang X, et al. 2014.. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. . Cell Res. 24:(2):177–89
     [Crossref] [Google Scholar]
  91. 91.
    Patil DP, Chen C-K, Pickering BF, Chow A, Jackson C, et al. 2016.. m6A RNA methylation promotes XIST-mediated transcriptional repression. . Nature 537:(7620):369–73
     [Crossref] [Google Scholar]
  92. 92.
    Yue Y, Liu J, Cui X, Cao J, Luo G, et al. 2018.. VIRMA mediates preferential m6A mRNA methylation in 3′UTR and near stop codon and associates with alternative polyadenylation. . Cell Discov. 4::10
     [Crossref] [Google Scholar]
  93. 93.
    Wen J, Lv R, Ma H, Shen H, He C, et al. 2018.. Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell self-renewal. . Mol. Cell 69:(6):1028–38.e6
     [Crossref] [Google Scholar]
  94. 94.
    Pandolfini L, Barbieri I, Bannister AJ, Hendrick A, Andrews B, et al. 2019.. METTL1 promotes let-7 microRNA processing via m7G methylation. . Mol. Cell 74:(6):1278–90.e9
     [Crossref] [Google Scholar]
  95. 95.
    Zhang L-S, Liu C, Ma H, Dai Q, Sun H-L, et al. 2019.. Transcriptome-wide mapping of internal N7-methylguanosine methylome in mammalian mRNA. . Mol. Cell 74:(6):1304–16.e8
     [Crossref] [Google Scholar]
  96. 96.
    Li J, Wang L, Hahn Q, Nowak RP, Viennet T, et al. 2023.. Structural basis of regulated m7G tRNA modification by METTL1–WDR4. . Nature 613:(7943):391–97
     [Crossref] [Google Scholar]
  97. 97.
    Leulliot N, Chaillet M, Durand D, Ulryck N, Blondeau K, van Tilbeurgh H. 2008.. Structure of the yeast tRNA m7G methylation complex. . Structure 16:(1):52–61
     [Crossref] [Google Scholar]
  98. 98.
    Ruiz-Arroyo VM, Raj R, Babu K, Onolbaatar O, Roberts PH, Nam Y. 2023.. Structures and mechanisms of tRNA methylation by METTL1–WDR4. . Nature 613:(7943):383–90
     [Crossref] [Google Scholar]
  99. 99.
    Jin X, Guan Z, Hu N, He C, Yin P, et al. 2023.. Structural insight into how WDR4 promotes the tRNA N7-methylguanosine methyltransferase activity of METTL1. . Cell Discov. 9:(1):65
     [Crossref] [Google Scholar]
  100. 100.
    Cartlidge RA, Knebel A, Peggie M, Alexandrov A, Phizicky EM, Cohen P. 2005.. The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells. . EMBO J. 24:(9):1696–705
     [Crossref] [Google Scholar]
  101. 101.
    Bourgeois G, Létoquart J, van Tran N, Graille M. 2017.. Trm112, a protein activator of methyltransferases modifying actors of the eukaryotic translational apparatus. . Biomolecules 7:(1):7
     [Crossref] [Google Scholar]
  102. 102.
    Brūmele B, Mutso M, Telanne L, Õunap K, Spunde K, et al. 2021.. Human TRMT112-methyltransferase network consists of seven partners interacting with a common co-factor. . Int. J. Mol. Sci. 22:(24):13593
     [Crossref] [Google Scholar]
  103. 103.
    Liger D, Mora L, Lazar N, Figaro S, Henri J, et al. 2011.. Mechanism of activation of methyltransferases involved in translation by the Trm112 “hub” protein. . Nucleic Acids Res. 39:(14):624959. Erratum . 2016.. Nucleic Acids Res. 44:(3):1482
     [Google Scholar]
  104. 104.
    Wang C, van Tran N, Jactel V, Guérineau V, Graille M. 2020.. Structural and functional insights into Archaeoglobus fulgidus m2G10 tRNA methyltransferase Trm11 and its Trm112 activator. . Nucleic Acids Res. 48:(19):11068–82
     [Crossref] [Google Scholar]
  105. 105.
    Létoquart J, van Tran N, Caroline V, Aleksandrov A, Lazar N, et al. 2015.. Insights into molecular plasticity in protein complexes from Trm9–Trm112 tRNA modifying enzyme crystal structure. . Nucleic Acids Res. 43:(22):10989–1002
     [Crossref] [Google Scholar]
  106. 106.
    Létoquart J, Huvelle E, Wacheul L, Bourgeois G, Zorbas C, et al. 2014.. Structural and functional studies of Bud23–Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes. . PNAS 111:(51):E5518–26
     [Crossref] [Google Scholar]
  107. 107.
    Bourgeois G, Marcoux J, Saliou J-M, Cianférani S, Graille M. 2017.. Activation mode of the eukaryotic m2G10 tRNA methyltransferase Trm11 by its partner protein Trm112. . Nucleic Acids Res. 45:(4):1971–82
     [Google Scholar]
  108. 108.
    Guy MP, Podyma BM, Preston MA, Shaheen HH, Krivos KL, et al. 2012.. Yeast Trm7 interacts with distinct proteins for critical modifications of the tRNAPhe anticodon loop. . RNA 18:(10):1921–33
     [Crossref] [Google Scholar]
  109. 109.
    Li J, Wang Y-N, Xu B-S, Liu Y-P, Zhou M, et al. 2020.. Intellectual disability-associated gene ftsj1 is responsible for 2′-O-methylation of specific tRNAs. . EMBO Rep. 21:(8):e50095
     [Crossref] [Google Scholar]
  110. 110.
    Guy MP, Phizicky EM. 2015.. Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes. . RNA 21:(1):61–74
     [Crossref] [Google Scholar]
  111. 111.
    Hirata A, Okada K, Yoshii K, Shiraishi H, Saijo S, et al. 2019.. Structure of tRNA methyltransferase complex of Trm7 and Trm734 reveals a novel binding interface for tRNA recognition. . Nucleic Acids Res. 47:(20):10942–55
     [Crossref] [Google Scholar]
  112. 112.
    Lentini JM, Alsaif HS, Faqeih E, Alkuraya FS, Fu D. 2020.. DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification. . Nat. Commun. 11:(1):2510
     [Crossref] [Google Scholar]
  113. 113.
    Muthmann N, Albers M, Rentmeister A. 2023.. CAPturAM, a chemo-enzymatic strategy for selective enrichment and detection of physiological CAPAM-targets. . Angew. Chem. Int. Ed. 62:(4):e202211957
     [Crossref] [Google Scholar]
  114. 114.
    Weissenboeck FP, Schepers H, Rentmeister A. 2023.. Optochemical control of mRNA translation in eukaryotes. . Angew. Chem. Int. Ed. 62:(23):e202301778
     [Crossref] [Google Scholar]
  115. 115.
    Kawai G, Yamamoto Y, Kamimura T, Masegi T, Sekine M, et al. 1992.. Conformational rigidity of specific pyrimidine residues in tRNA arises from posttranscriptional modifications that enhance steric interaction between the base and the 2′-hydroxyl group. . Biochemistry 31:(4):1040–46
     [Crossref] [Google Scholar]
  116. 116.
    Prusiner P, Yathindra N, Sundaralingam M. 1974.. Effect of ribose O(2′)-methylation on the conformation of nucleosides and nucleotides. . Biochim. Biophys. Acta Nucleic Acids Protein Synth. 366:(2):115–23
     [Crossref] [Google Scholar]
  117. 117.
    Marbaniang CN, Vogel J. 2016.. Emerging roles of RNA modifications in bacteria. . Curr. Opin. Microbiol. 30::50–57
     [Crossref] [Google Scholar]
  118. 118.
    Höfler S, Carlomagno T. 2020.. Structural and functional roles of 2′-O-ribose methylations and their enzymatic machinery across multiple classes of RNAs. . Curr. Opin. Struct. Biol. 65::42–50
     [Crossref] [Google Scholar]
  119. 119.
    Decatur WA, Fournier MJ. 2002.. rRNA modifications and ribosome function. . Trends Biochem. Sci. 27:(7):344–51
     [Crossref] [Google Scholar]
  120. 120.
    Watkins NJ, Bohnsack MT. 2012.. The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA. . WIREs RNA 3:(3):397–414
     [Crossref] [Google Scholar]
  121. 121.
    Kiss-László Z, Henry Y, Bachellerie JP, Caizergues-Ferrer M, Kiss T. 1996.. Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. . Cell 85:(7):1077–88
     [Crossref] [Google Scholar]
  122. 122.
    Ha M, Kim VN. 2014.. Regulation of microRNA biogenesis. . Nat. Rev. Mol. Cell Biol. 15:(8):509–24
     [Crossref] [Google Scholar]
  123. 123.
    Adli M. 2018.. The CRISPR tool kit for genome editing and beyond. . Nat. Commun. 9:(1):1911
     [Crossref] [Google Scholar]
  124. 124.
    Hoeppner MP, Poole AM. 2012.. Comparative genomics of eukaryotic small nucleolar RNAs reveals deep evolutionary ancestry amidst ongoing intragenomic mobility. . BMC Evol. Biol. 12::183
     [Crossref] [Google Scholar]
  125. 125.
    Tollervey D, Lehtonen H, Jansen R, Kern H, Hurt EC. 1993.. Temperature-sensitive mutations demonstrate roles for yeast fibrillarin in pre-rRNA processing, pre-rRNA methylation, and ribosome assembly. . Cell 72:(3):443–57
     [Crossref] [Google Scholar]
  126. 126.
    Tycowski KT, You ZH, Graham PJ, Steitz JA. 1998.. Modification of U6 spliceosomal RNA is guided by other small RNAs. . Mol. Cell 2:(5):629–38
     [Crossref] [Google Scholar]
  127. 127.
    Reichow SL, Hamma T, Ferré-D'Amaré AR, Varani G. 2007.. The structure and function of small nucleolar ribonucleoproteins. . Nucleic Acids Res. 35:(5):1452–64
     [Crossref] [Google Scholar]
  128. 128.
    Watkins NJ, Ségault V, Charpentier B, Nottrott S, Fabrizio P, et al. 2000.. A common core RNP structure shared between the small nucleoar box C/D RNPs and the spliceosomal U4 snRNP. . Cell 103:(3):457–66
     [Crossref] [Google Scholar]
  129. 129.
    Shi Y, El-Deeb IM, Masic V, Hartley-Tassell L, Maggioni A, et al. 2021.. Discovery of cofactor competitive inhibitors against the human methyltransferase fibrillarin. . Pharmaceuticals 15:(1):26
     [Crossref] [Google Scholar]
  130. 130.
    Lin J, Lai S, Jia R, Xu A, Zhang L, et al. 2011.. Structural basis for site-specific ribose methylation by box C/D RNA protein complexes. . Nature 469:(7331):559–63
     [Crossref] [Google Scholar]
  131. 131.
    Schapira M. 2016.. Structural chemistry of human RNA methyltransferases. . ACS Chem. Biol. 11:(3):575–82
     [Crossref] [Google Scholar]
  132. 132.
    Werner M, Purta E, Kaminska KH, Cymerman IA, Campbell DA, et al. 2011.. 2′-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. . Nucleic Acids Res. 39:(11):4756–68
     [Crossref] [Google Scholar]
  133. 133.
    Bélanger F, Stepinski J, Darzynkiewicz E, Pelletier J. 2010.. Characterization of hMTr1, a human Cap1 2′-O-ribose methyltransferase. . J. Biol. Chem. 285:(43):33037–44
     [Crossref] [Google Scholar]
  134. 134.
    Smietanski M, Werner M, Purta E, Kaminska KH, Stepinski J, et al. 2014.. Structural analysis of human 2′-O-ribose methyltransferases involved in mRNA cap structure formation. . Nat. Commun. 5:(1):3004
     [Crossref] [Google Scholar]
  135. 135.
    Singh S, Vanden Broeck A, Miller L, Chaker-Margot M, Klinge S. 2021.. Nucleolar maturation of the human small subunit processome. . Science 373:(6560):eabj5338
     [Crossref] [Google Scholar]
  136. 136.
    Yang Z, Wang J, Huang L, Lilley DMJ, Ye K. 2020.. Functional organization of box C/D RNA-guided RNA methyltransferase. . Nucleic Acids Res. 48:(9):5094–105
     [Crossref] [Google Scholar]
  137. 137.
    Hebras J, Krogh N, Marty V, Nielsen H, Cavaillé J. 2020.. Developmental changes of rRNA ribose methylations in the mouse. . RNA Biol. 17:(1):150–64
     [Crossref] [Google Scholar]
  138. 138.
    Jansson MD, Häfner SJ, Altinel K, Tehler D, Krogh N, et al. 2021.. Regulation of translation by site-specific ribosomal RNA methylation. . Nat. Struct. Mol. Biol. 28:(11):889–99
     [Crossref] [Google Scholar]
  139. 139.
    Krogh N, Jansson MD, Häfner SJ, Tehler D, Birkedal U, et al. 2016.. Profiling of 2′-O-Me in human rRNA reveals a subset of fractionally modified positions and provides evidence for ribosome heterogeneity. . Nucleic Acids Res. 44:(16):7884–95
     [Crossref] [Google Scholar]
  140. 140.
    Krogh N, Asmar F, Côme C, Munch-Petersen HF, Grønbæk K, Nielsen H. 2020.. Profiling of ribose methylations in ribosomal RNA from diffuse large B-cell lymphoma patients for evaluation of ribosomes as drug targets. . NAR Cancer 2:(4):zcaa035
     [Crossref] [Google Scholar]
  141. 141.
    Taoka M, Nobe Y, Yamaki Y, Sato K, Ishikawa H, et al. 2018.. Landscape of the complete RNA chemical modifications in the human 80S ribosome. . Nucleic Acids Res. 46:(18):9289–98
     [Crossref] [Google Scholar]
  142. 142.
    Buchhaupt M, Sharma S, Kellner S, Oswald S, Paetzold M, et al. 2014.. Partial methylation at Am100 in 18S rRNA of baker's yeast reveals ribosome heterogeneity on the level of eukaryotic rRNA modification. . PLOS ONE 9:(2):e89640
     [Crossref] [Google Scholar]
  143. 143.
    Aquino GRR, Krogh N, Hackert P, Martin R, Gallesio JD, et al. 2021.. RNA helicase-mediated regulation of snoRNP dynamics on pre-ribosomes and rRNA 2′-O-methylation. . Nucleic Acids Res. 49:(7):4066–84
     [Crossref] [Google Scholar]
  144. 144.
    Liang WQ, Fournier MJ. 1995.. U14 base-pairs with 18S rRNA: a novel snoRNA interaction required for rRNA processing. . Genes Dev. 9:(19):2433–43
     [Crossref] [Google Scholar]
  145. 145.
    Mitterer V, Pertschy B. 2022.. RNA folding and functions of RNA helicases in ribosome biogenesis. . RNA Biol. 19:(1):781–810
     [Crossref] [Google Scholar]
  146. 146.
    Jorjani H, Kehr S, Jedlinski DJ, Gumienny R, Hertel J, et al. 2016.. An updated human snoRNAome. . Nucleic Acids Res. 44:(11):5068–82
     [Crossref] [Google Scholar]
  147. 147.
    Dai Q, Moshitch-Moshkovitz S, Han D, Kol N, Amariglio N, et al. 2017.. Nm-seq maps 2′-O-methylation sites in human mRNA with base precision. . Nat. Methods 14:(7):695–98
     [Crossref] [Google Scholar]
  148. 148.
    Elliott BA, Ho H-T, Ranganathan SV, Vangaveti S, Ilkayeva O, et al. 2019.. Modification of messenger RNA by 2′-O-methylation regulates gene expression in vivo. . Nat. Commun. 10:(1):3401
     [Crossref] [Google Scholar]
  149. 149.
    Choi J, Indrisiunaite G, DeMirci H, Ieong K-W, Wang J, et al. 2018.. 2′-O-methylation in mRNA disrupts tRNA decoding during translation elongation. . Nat. Struct. Mol. Biol. 25:(3):208–16
     [Crossref] [Google Scholar]
  150. 150.
    Tessarz P, Santos-Rosa H, Robson SC, Sylvestersen KB, Nelson CJ, et al. 2014.. Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification. . Nature 505:(7484):564–68
     [Crossref] [Google Scholar]
  151. 151.
    Yao R-W, Xu G, Wang Y, Shan L, Luan P-F, et al. 2019.. Nascent pre-rRNA sorting via phase separation drives the assembly of dense fibrillar components in the human nucleolus. . Mol. Cell 76:(5):767–83.e11
     [Crossref] [Google Scholar]
  152. 152.
    Lafontaine DL, Bousquet-Antonelli C, Henry Y, Caizergues-Ferrer M, Tollervey D. 1998.. The box H+ACA snoRNAs carry Cbf5p, the putative rRNA pseudouridine synthase. . Genes Dev. 12:(4):527–37
     [Crossref] [Google Scholar]
  153. 153.
    Ganot P, Bortolin ML, Kiss T. 1997.. Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. . Cell 89:(5):799–809
     [Crossref] [Google Scholar]
  154. 154.
    Sharma S, Langhendries J-L, Watzinger P, Kötter P, Entian K-D, Lafontaine DLJ. 2015.. Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1. . Nucleic Acids Res. 43:(4):2242–58
     [Crossref] [Google Scholar]
  155. 155.
    Liu B, Ni J, Fournier MJ. 2001.. Probing RNA in vivo with methylation guide small nucleolar RNAs. . Methods 23:(3):276–86
     [Crossref] [Google Scholar]
  156. 156.
    Tomkuvienė M, Clouet-d'Orval B, Černiauskas I, Weinhold E, Klimašauskas S. 2012.. Programmable sequence-specific click-labeling of RNA using archaeal box C/D RNP methyltransferases. . Nucleic Acids Res. 40:(14):6765–73
     [Crossref] [Google Scholar]
  157. 157.
    Züst R, Cervantes-Barragan L, Habjan M, Maier R, Neuman BW, et al. 2011.. Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. . Nat. Immunol. 12:(2):137–43
     [Crossref] [Google Scholar]
  158. 158.
    Jadhav VR, Yarus M. 2002.. Coenzymes as coribozymes. . Biochimie 84:(9):877–88
     [Crossref] [Google Scholar]
  159. 159.
    Breaker RR. 2020.. Imaginary ribozymes. . ACS Chem. Biol. 15:(8):2020–30
     [Crossref] [Google Scholar]
  160. 160.
    Batey RT. 2011.. Recognition of S-adenosylmethionine by riboswitches. . WIREs RNA 2:(2):299–311
     [Crossref] [Google Scholar]
  161. 161.
    Wilson C, Szostak JW. 1995.. In vitro evolution of a self-alkylating ribozyme. . Nature 374:(6525):777–82
     [Crossref] [Google Scholar]
  162. 162.
    Burke DH, Gold L. 1997.. RNA aptamers to the adenosine moiety of S-adenosyl methionine: structural inferences from variations on a theme and the reproducibility of SELEX. . Nucleic Acids Res. 25:(10):2020–24
     [Crossref] [Google Scholar]
  163. 163.
    Scheitl CPM, Ghaem Maghami M, Lenz A-K, Höbartner C. 2020.. Site-specific RNA methylation by a methyltransferase ribozyme. . Nature 587:(7835):663–67
     [Crossref] [Google Scholar]
  164. 164.
    Scheitl CPM, Mieczkowski M, Schindelin H, Höbartner C. 2022.. Structure and mechanism of the methyltransferase ribozyme MTR1. . Nat. Chem. Biol. 18:(5):547–55
     [Crossref] [Google Scholar]
  165. 165.
    Deng J, Wilson TJ, Wang J, Peng X, Li M, et al. 2022.. Structure and mechanism of a methyltransferase ribozyme. . Nat. Chem. Biol. 18:(5):556–64
     [Crossref] [Google Scholar]
  166. 166.
    Liu Y, Zhou J, Li X, Zhang X, Shi J, et al. 2022.. tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. . Nat. Immunol. 23:(10):1433–44
     [Crossref] [Google Scholar]
  167. 167.
    Flemmich L, Heel S, Moreno S, Breuker K, Micura R. 2021.. A natural riboswitch scaffold with self-methylation activity. . Nat. Commun. 12:(1):3877
     [Crossref] [Google Scholar]
  168. 168.
    Jiang H, Gao Y, Zhang L, Chen D, Gan J, Murchie AIH. 2021.. The identification and characterization of a selected SAM-dependent methyltransferase ribozyme that is present in natural sequences. . Nat. Catal. 4:(10):872–81
     [Crossref] [Google Scholar]
  169. 169.
    Jumper J, Evans R, Pritzel A, Green T, Figurnov M, et al. 2021.. Highly accurate protein structure prediction with AlphaFold. . Nature 596:(7873):583–89
     [Crossref] [Google Scholar]
  170. 170.
    Cross R. 2019.. Epitranscriptomics: the new RNA code and the race to drug it. . Chemical & Engineering News, Feb. 18. https://cen.acs.org/business/start-ups/Epitranscriptomics-new-RNA-code-race/97/i7#:∼:text=A%20series%20of%20discoveries%20and,erase%2C%20and%20read%20these%20modifications
    [Google Scholar]
  171. 171.
    Schubert C. 2019.. Epitranscriptomics: RNA revisited. . Science Cust. Publ., May 17. https://www.science.org/content/article/epitranscriptomics-rna-revisited
    [Google Scholar]
  172. 172.
    Tsukamoto Y, Hiono T, Yamada S, Matsuno K, Faist A, et al. 2023.. Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication. . Science 379:(6632):586–91
     [Crossref] [Google Scholar]
  173. 173.
    Ramdhan P, Li C. 2022.. Targeting viral methyltransferases: an approach to antiviral treatment for ssRNA viruses. . Viruses 14:(2):379
     [Crossref] [Google Scholar]
  174. 174.
    Bergant V, Yamada S, Grass V, Tsukamoto Y, Lavacca T, et al. 2022.. Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2′-O-ribose methyltransferases. . EMBO J. 41:(17):e111608
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-biochem-030222-112310
Loading
How Natural Enzymes and Synthetic Ribozymes Generate Methylated Nucleotides in RNA
Annual Review of Biochemistry 93, 109 (2024); https://doi.org/10.1146/annurev-biochem-030222-112310
/content/journals/10.1146/annurev-biochem-030222-112310
/content/journals/10.1146/annurev-biochem-030222-112310
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error