Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Structural and evolutionary insights into ribosomal RNA methylation

Nature Chemical Biology volume 14, pages 226–235 (2018)Cite this article

Subjects

Abstract

Methylation of nucleotides in ribosomal RNAs (rRNAs) is a ubiquitous feature that occurs in all living organisms. Identification of all enzymes responsible for rRNA methylation, as well as mapping of all modified rRNA residues, is now complete for a number of model species, such as Escherichia coli and Saccharomyces cerevisiae. Recent high-resolution structures of bacterial ribosomes provided the first direct visualization of methylated nucleotides. The structures of ribosomes from various organisms and organelles have also lately become available, enabling comparative structure-based analysis of rRNA methylation sites in various taxonomic groups. In addition to the conserved core of modified residues in ribosomes from the majority of studied organisms, structural analysis points to the functional roles of some of the rRNA methylations, which are discussed in this Review in an evolutionary context.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Functional elements of the bacterial ribosome.
Figure 2: Chemical structures of modified and unmodified rRNA nucleosides.
Figure 3: Modification sites in ribosomal RNAs.
Figure 4: Universally conserved rRNA-methylation sites in the small and large ribosomal subunits.
Figure 5: Molecular contacts of modified nucleotides with the ribosome ligands and within the ribosome structure.
Figure 6: Reciprocally methylated nucleotide pairs found in various taxonomic groups.
Figure 7: Examples of convergent and divergent evolution of rRNA and tRNA methylation systems.

Similar content being viewed by others

Accession codes

Accessions

Protein Data Bank

References

  1. Machnicka, M.A. et al. MODOMICS: a database of RNA modification pathways--2013 update. Nucleic Acids Res. 41, D262–D267 (2013). Ref. 1 contains an update to the comprehensive database of known types of RNA modifications, the chemical structures of modified ribonucleosides, their biosynthetic pathways, RNA-modifying enzymes and the location of modified residues in RNA sequences.

    Article  CAS  PubMed  Google Scholar 

  2. Seistrup, K.H. et al. Bypassing rRNA methylation by RsmA/Dim1during ribosome maturation in the hyperthermophilic archaeon Nanoarchaeum equitans. Nucleic Acids Res. 45, 2007–2015 (2017).

    CAS  PubMed  Google Scholar 

  3. Piekna-Przybylska, D., Decatur, W.A. & Fournier, M.J. The 3D rRNA modification maps database: with interactive tools for ribosome analysis. Nucleic Acids Res. 36, D178–D183 (2008).

    CAS  PubMed  Google Scholar 

  4. Fu, Y., Dominissini, D., Rechavi, G. & He, C. Gene expression regulation mediated through reversible m6A RNA methylation. Nat. Rev. Genet. 15, 293–306 (2014).

    CAS  PubMed  Google Scholar 

  5. Meyer, K.D. & Jaffrey, S.R. Rethinking m6A readers, writers, and erasers. Annu. Rev. Cell Dev. Biol. 33, 319–342 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Golovina, A.Y. et al. The last rRNA methyltransferase of E. coli revealed: the yhiR gene encodes adenine-N6 methyltransferase specific for modification of A2030 of 23S ribosomal RNA. RNA 18, 1725–1734 (2012). With the work in ref. 6 , the list of E. coli rRNA methyltransferases is completed. It allows conducting a comprehensive analysis of the entire rRNA methylation system in the most studied model organism.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Sharma, S. & Lafontaine, D.L. 'View from a bridge': a new perspective on eukaryotic rRNA base modification. Trends Biochem. Sci. 40, 560–575 (2015).

    CAS  PubMed  Google Scholar 

  8. Liu, M. & Douthwaite, S. Methylation at nucleotide G745 or G748 in 23S rRNA distinguishes Gram-negative from Gram-positive bacteria. Mol. Microbiol. 44, 195–204 (2002).

    CAS  PubMed  Google Scholar 

  9. Desmolaize, B. et al. A single methyltransferase YefA (RlmCD) catalyses both m5U747 and m5U1939 modifications in Bacillus subtilis 23S rRNA. Nucleic Acids Res. 39, 9368–9375 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Lartigue, C. et al. The flavoprotein Mcap0476 (RlmFO) catalyzes m5U1939 modification in Mycoplasma capricolum 23S rRNA. Nucleic Acids Res. 42, 8073–8082 (2014). Refs. 9 and 10 describe examples of the divergent and convergent evolution of rRNA methyltransferases, respectively.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Guymon, R., Pomerantz, S.C., Crain, P.F. & McCloskey, J.A. Influence of phylogeny on posttranscriptional modification of rRNA in thermophilic prokaryotes: the complete modification map of 16S rRNA of Thermus thermophilus. Biochemistry 45, 4888–4899 (2006).

    CAS  PubMed  Google Scholar 

  12. Schosserer, M. et al. Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat. Commun. 6, 6158 (2015).

    CAS  PubMed  Google Scholar 

  13. Wurm, J.P. et al. The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N1-specific methyltransferase. Nucleic Acids Res. 38, 2387–2398 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Meyer, B. et al. 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, 1526–1537 (2011).

    CAS  PubMed  Google Scholar 

  15. Meyer, B. et al. Ribosome biogenesis factor Tsr3 is the aminocarboxypropyl transferase responsible for 18S rRNA hypermodification in yeast and humans. Nucleic Acids Res. 44, 4304–4316 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Zorbas, C. et al. The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis. Mol. Biol. Cell 26, 2080–2095 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Waku, T. et al. NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner. J. Cell Sci. 129, 2382–2393 (2016).

    CAS  PubMed  Google Scholar 

  18. Polikanov, Y.S., Melnikov, S.V., Söll, D. & Steitz, T.A. Structural insights into the role of rRNA modifications in protein synthesis and ribosome assembly. Nat. Struct. Mol. Biol. 22, 342–344 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Noeske, J. et al. High-resolution structure of the Escherichia coli ribosome. Nat. Struct. Mol. Biol. 22, 336–341 (2015). These studies describe structures of the bacterial 70S ribosomes either from T. thermophilus (ref. 18 ) or E. coli (ref. 19 ) that allowed, for the first time, the visualization of every individual nucleotide modification in the bacterial ribosomes at the highest resolution reported to date.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Ben-Shem, A. et al. The structure of the eukaryotic ribosome at 3.0 Å resolution. Science 334, 1524–1529 (2011). The study in ref. 20 reports the first crystal structure of the 80S ribosome from yeast S. cerevisiae.

    CAS  PubMed  Google Scholar 

  21. Khatter, H., Myasnikov, A.G., Natchiar, S.K. & Klaholz, B.P. Structure of the human 80S ribosome. Nature 520, 640–645 (2015). The study in ref. 21 reports the highest-resolution cryo-EM structure of the 80S ribosome from human.

    CAS  PubMed  Google Scholar 

  22. Anger, A.M. et al. Structures of the human and Drosophila 80S ribosome. Nature 497, 80–85 (2013). The study in ref. 22 reports the first cryo-EM structure of the 80S ribosome from human.

    CAS  PubMed  Google Scholar 

  23. Amunts, A., Brown, A., Toots, J., Scheres, S.H.W. & Ramakrishnan, V. Ribosome. The structure of the human mitochondrial ribosome. Science 348, 95–98 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Desai, N., Brown, A., Amunts, A. & Ramakrishnan, V. The structure of the yeast mitochondrial ribosome. Science 355, 528–531 (2017). The first two cryo-EM structures of the complete ribosomes from human and yeast mitochondria are reported in refs. 23 and 24, respectively.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Sergiev, P.V. et al. in Ribosomes (eds. Rodnina, M.V., Wintermeyer, W. & Green, R.) 97–110 (Springer Vienna, 2011).

    Google Scholar 

  26. Siibak, T. & Remme, J. Subribosomal particle analysis reveals the stages of bacterial ribosome assembly at which rRNA nucleotides are modified. RNA 16, 2023–2032 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Kiss-László, Z., Henry, Y., Bachellerie, J.P., Caizergues-Ferrer, M. & Kiss, T. Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell 85, 1077–1088 (1996).

    PubMed  Google Scholar 

  28. Ni, J., Tien, A.L. & Fournier, M.J. Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell 89, 565–573 (1997).

    CAS  PubMed  Google Scholar 

  29. Yang, J. et al. Mapping of complete set of ribose and base modifications of yeast rRNA by RP-HPLC and mung bean nuclease assay. PLoS One 11, e0168873 (2016) Ref. 29 completes mapping of all modified residues within yeast rRNA.

    PubMed  PubMed Central  Google Scholar 

  30. Piekna-Przybylska, D., Decatur, W.A. & Fournier, M.J. New bioinformatic tools for analysis of nucleotide modifications in eukaryotic rRNA. RNA 13, 305–312 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lestrade, L. & Weber, M.J. snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res. 34, D158–D162 (2006).

    CAS  PubMed  Google Scholar 

  32. Kirpekar, F., Hansen, L.H., Rasmussen, A., Poehlsgaard, J. & Vester, B. The archaeon Haloarcula marismortui has few modifications in the central parts of its 23S ribosomal RNA. J. Mol. Biol. 348, 563–573 (2005).

    CAS  PubMed  Google Scholar 

  33. Sloan, K.E. et al. Tuning the ribosome: the influence of rRNA modification on eukaryotic ribosome biogenesis and function. RNA Biol. 14, 1138–1152 (2017).

    PubMed  Google Scholar 

  34. Demirci, H. et al. Modification of 16S ribosomal RNA by the KsgA methyltransferase restructures the 30S subunit to optimize ribosome function. RNA 16, 2319–2324 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Baudin-Baillieu, A. et al. Nucleotide modifications in three functionally important regions of the Saccharomyces cerevisiae ribosome affect translation accuracy. Nucleic Acids Res. 37, 7665–7677 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Prokhorova, I.V. et al. Modified nucleotides m2G966/m5C967 of Escherichia coli 16S rRNA are required for attenuation of tryptophan operon. Sci. Rep. 3, 3236 (2013).

    PubMed  PubMed Central  Google Scholar 

  37. van Buul, C.P., Visser, W. & van Knippenberg, P.H. Increased translational fidelity caused by the antibiotic kasugamycin and ribosomal ambiguity in mutants harbouring the ksgA gene. FEBS Lett. 177, 119–124 (1984).

    CAS  PubMed  Google Scholar 

  38. Okamoto, S. et al. Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Mol. Microbiol. 63, 1096–1106 (2007).

    CAS  PubMed  Google Scholar 

  39. Popova, A.M. & Williamson, J.R. Quantitative analysis of rRNA modifications using stable isotope labeling and mass spectrometry. J. Am. Chem. Soc. 136, 2058–2069 (2014). Ref. 39 has evidence for the temporal pattern of rRNA modifications that occur during the assembly of ribosomal subunits.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Birkedal, U. et al. Profiling of ribose methylations in RNA by high-throughput sequencing. Angew. Chem. Int. Edn Engl. 54, 451–455 (2015).

    CAS  Google Scholar 

  41. Kornprobst, M. et al. Architecture of the 90S pre-ribosome: a structural view on the birth of the eukaryotic ribosome. Cell 166, 380–393 (2016).

    CAS  PubMed  Google Scholar 

  42. Sloan, K.E. et al. The association of late-acting snoRNPs with human pre-ribosomal complexes requires the RNA helicase DDX21. Nucleic Acids Res. 43, 553–564 (2015).

    CAS  PubMed  Google Scholar 

  43. Lapeyre, B. & Purushothaman, S.K. Spb1p-directed formation of Gm2922 in the ribosome catalytic center occurs at a late processing stage. Mol. Cell 16, 663–669 (2004).

    CAS  PubMed  Google Scholar 

  44. Létoquart, J. et al. Structural and functional studies of Bud23-Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes. Proc. Natl. Acad. Sci. USA 111, E5518–E5526 (2014).

    PubMed  PubMed Central  Google Scholar 

  45. Maden, E.H. & Wakeman, J.A. Pseudouridine distribution in mammalian 18S ribosomal RNA. A major cluster in the central region of the molecule. Biochem. J. 249, 459–464 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Samarsky, D.A., Balakin, A.G. & Fournier, M.J. Characterization of three new snRNAs from Saccharomyces cerevisiae: snR34, snR35 and snR36. Nucleic Acids Res. 23, 2548–2554 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Arenz, S. & Wilson, D.N. Blast from the past: reassessing forgotten translation inhibitors, antibiotic selectivity, and resistance mechanisms to aid drug development. Mol. Cell 61, 3–14 (2016).

    CAS  PubMed  Google Scholar 

  48. Armistead, J. et al. Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-Conradi syndrome. Am. J. Hum. Genet. 84, 728–739 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Oie, S. et al. Hepatic rRNA transcription regulates high-fat-diet-induced obesity. Cell Rep. 7, 807–820 (2014).

    CAS  PubMed  Google Scholar 

  50. Koeck, T. et al. A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes. Cell Metab. 13, 80–91 (2011).

    CAS  PubMed  Google Scholar 

  51. Bourgeois, G. et al. Eukaryotic rRNA modification by yeast 5-methylcytosine-methyltransferases and human proliferation-associated antigen p120. PLoS One 10, e0133321 (2015).

    PubMed  PubMed Central  Google Scholar 

  52. Poldermans, B., Roza, L. & Van Knippenberg, P.H. Studies on the function of two adjacent N6,N6-dimethyladenosines near the 3′ end of 16S ribosomal RNA of Escherichia coli. III. Purification and properties of the methylating enzyme and methylase-30S interactions. J. Biol. Chem. 254, 9094–9100 (1979).

    CAS  PubMed  Google Scholar 

  53. Lafontaine, D., Delcour, J., Glasser, A.L., Desgrès, J. & Vandenhaute, J. The DIM1 gene responsible for the conserved m62Am62A dimethylation in the 3′-terminal loop of 18S rRNA is essential in yeast. J. Mol. Biol. 241, 492–497 (1994).

    CAS  PubMed  Google Scholar 

  54. Seidel-Rogol, B.L., McCulloch, V. & Shadel, G.S. Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop. Nat. Genet. 33, 23–24 (2003).

    CAS  PubMed  Google Scholar 

  55. Cotney, J., McKay, S.E. & Shadel, G.S. Elucidation of separate, but collaborative functions of the rRNA methyltransferase-related human mitochondrial transcription factors B1 and B2 in mitochondrial biogenesis reveals new insight into maternally inherited deafness. Hum. Mol. Genet. 18, 2670–2682 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Connolly, K., Rife, J.P. & Culver, G. Mechanistic insight into the ribosome biogenesis functions of the ancient protein KsgA. Mol. Microbiol. 70, 1062–1075 (2008). The study in ref. 56 reports the first evidence of the second function of KsgA methyltransferase as ribosome assembly factor.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lafontaine, D., Vandenhaute, J. & Tollervey, D. The 18S rRNA dimethylase Dim1p is required for pre-ribosomal RNA processing in yeast. Genes Dev. 9, 2470–2481 (1995).

    CAS  PubMed  Google Scholar 

  58. White, J. et al. Bud23 methylates G1575 of 18S rRNA and is required for efficient nuclear export of pre-40S subunits. Mol. Cell. Biol. 28, 3151–3161 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Haag, S., Kretschmer, J. & Bohnsack, M.T. WBSCR22/Merm1 is required for late nuclear pre-ribosomal RNA processing and mediates N7-methylation of G1639 in human 18S rRNA. RNA 21, 180–187 (2015).

    PubMed  PubMed Central  Google Scholar 

  60. Lövgren, J.M. & Wikström, P.M. The rlmB gene is essential for formation of Gm2251 in 23S rRNA but not for ribosome maturation in Escherichia coli. J. Bacteriol. 183, 6957–6960 (2001).

    PubMed  PubMed Central  Google Scholar 

  61. Caldas, T. et al. The FtsJ/RrmJ heat shock protein of Escherichia coli is a 23S ribosomal RNA methyltransferase. J. Biol. Chem. 275, 16414–16419 (2000).

    CAS  PubMed  Google Scholar 

  62. Tan, J., Jakob, U. & Bardwell, J.C. Overexpression of two different GTPases rescues a null mutation in a heat-induced rRNA methyltransferase. J. Bacteriol. 184, 2692–2698 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Pintard, L., Bujnicki, J.M., Lapeyre, B. & Bonnerot, C. MRM2 encodes a novel yeast mitochondrial 21S rRNA methyltransferase. EMBO J. 21, 1139–1147 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Lesnyak, D.V. et al. Methyltransferase that modifies guanine 966 of the 16S rRNA: functional identification and tertiary structure. J. Biol. Chem. 282, 5880–5887 (2007).

    CAS  PubMed  Google Scholar 

  65. Tscherne, J.S. et al. Purification, cloning, and characterization of the 16S RNA m5C967 methyltransferase from Escherichia coli. Biochemistry 38, 1884–1892 (1999).

    CAS  PubMed  Google Scholar 

  66. Arora, S. et al. Distinctive contributions of the ribosomal P-site elements m2G966, m5C967 and the C-terminal tail of the S9 protein in the fidelity of initiation of translation in Escherichia coli. Nucleic Acids Res. 41, 4963–4975 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Burakovsky, D.E. et al. Impact of methylations of m2G966/m5C967 in 16S rRNA on bacterial fitness and translation initiation. Nucleic Acids Res. 40, 7885–7895 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Kimura, S. & Suzuki, T. Fine-tuning of the ribosomal decoding center by conserved methyl-modifications in the Escherichia coli 16S rRNA. Nucleic Acids Res. 38, 1341–1352 (2010).

    CAS  PubMed  Google Scholar 

  69. Toh, S.M., Xiong, L., Bae, T. & Mankin, A.S. The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA. RNA 14, 98–106 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Giessing, A.M. et al. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 15, 327–336 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Polikanov, Y.S. et al. Distinct tRNA accommodation intermediates observed on the ribosome with the antibiotics Hygromycin A and A201A. Mol. Cell 58, 832–844 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Kimura, S., Sakai, Y., Ishiguro, K. & Suzuki, T. Biogenesis and iron-dependency of ribosomal RNA hydroxylation. Nucleic Acids Res. 45, 12974–12986 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Maden, B.E. Locations of methyl groups in 28S rRNA of Xenopus laevis and man. Clustering in the conserved core of molecule. J. Mol. Biol. 201, 289–314 (1988).

    CAS  PubMed  Google Scholar 

  74. Raychaudhuri, S., Conrad, J., Hall, B.G. & Ofengand, J. A pseudouridine synthase required for the formation of two universally conserved pseudouridines in ribosomal RNA is essential for normal growth of Escherichia coli. RNA 4, 1407–1417 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Urbonavicius, J., Skouloubris, S., Myllykallio, H. & Grosjean, H. Identification of a novel gene encoding a flavin-dependent tRNA:m5U methyltransferase in bacteria--evolutionary implications. Nucleic Acids Res. 33, 3955–3964 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Madsen, C.T., Mengel-Jørgensen, J., Kirpekar, F. & Douthwaite, S. Identifying the methyltransferases for m5U747 and m5U1939 in 23S rRNA using MALDI mass spectrometry. Nucleic Acids Res. 31, 4738–4746 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Chujo, T. & Suzuki, T. Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs. RNA 18, 2269–2276 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Bar-Yaacov, D. et al. Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates. PLoS Biol. 14, e1002557 (2016).

    PubMed  PubMed Central  Google Scholar 

  79. Balakin, A.G., Schneider, G.S., Corbett, M.S., Ni, J. & Fournier, M.J. SnR31, snR32, and snR33: three novel, non-essential snRNAs from Saccharomyces cerevisiae. Nucleic Acids Res. 21, 5391–5397 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Tscherne, J.S., Nurse, K., Popienick, P. & Ofengand, J. Purification, cloning, and characterization of the 16S RNA m2G1207 methyltransferase from Escherichia coli. J. Biol. Chem. 274, 924–929 (1999).

    CAS  PubMed  Google Scholar 

  81. Lowe, T.M. & Eddy, S.R. A computational screen for methylation guide snoRNAs in yeast. Science 283, 1168–1171 (1999).

    CAS  PubMed  Google Scholar 

  82. Metodiev, M.D. et al. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet. 10, e1004110 (2014).

    PubMed  PubMed Central  Google Scholar 

  83. Andersen, N.M. & Douthwaite, S. YebU is a m5C methyltransferase specific for 16S rRNA nucleotide 1407. J. Mol. Biol. 359, 777–786 (2006).

    CAS  PubMed  Google Scholar 

  84. Basturea, G.N., Rudd, K.E. & Deutscher, M.P. Identification and characterization of RsmE, the founding member of a new RNA base methyltransferase family. RNA 12, 426–434 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Basturea, G.N., Dague, D.R., Deutscher, M.P. & Rudd, K.E. YhiQ is RsmJ, the methyltransferase responsible for methylation of G1516 in 16S rRNA of E. coli. J. Mol. Biol. 415, 16–21 (2012).

    CAS  PubMed  Google Scholar 

  86. Peifer, C. et al. Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA. Nucleic Acids Res. 41, 1151–1163 (2013).

    CAS  PubMed  Google Scholar 

  87. Gustafsson, C. & Persson, B.C. Identification of the rrmA gene encoding the 23S rRNA m1G745 methyltransferase in Escherichia coli and characterization of an m1G745-deficient mutant. J. Bacteriol. 180, 359–365 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Sergiev, P.V., Serebryakova, M.V., Bogdanov, A.A. & Dontsova, O.A. The ybiN gene of Escherichia coli encodes adenine-N6 methyltransferase specific for modification of A1618 of 23S ribosomal RNA, a methylated residue located close to the ribosomal exit tunnel. J. Mol. Biol. 375, 291–300 (2008).

    CAS  PubMed  Google Scholar 

  89. Sharma, S., Watzinger, P., Kötter, P. & Entian, K.D. Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 41, 5428–5443 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Sergiev, P.V., Lesnyak, D.V., Bogdanov, A.A. & Dontsova, O.A. Identification of Escherichia coli m2G methyltransferases: II. The ygjO gene encodes a methyltransferase specific for G1835 of the 23S rRNA. J. Mol. Biol. 364, 26–31 (2006).

    CAS  PubMed  Google Scholar 

  91. Purta, E., Kaminska, K.H., Kasprzak, J.M., Bujnicki, J.M. & Douthwaite, S. YbeA is the m3Psi methyltransferase RlmH that targets nucleotide 1915 in 23S rRNA. RNA 14, 2234–2244 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Badis, G., Fromont-Racine, M. & Jacquier, A. A snoRNA that guides the two most conserved pseudouridine modifications within rRNA confers a growth advantage in yeast. RNA 9, 771–779 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Ganot, P., Bortolin, M.L. & Kiss, T. Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell 89, 799–809 (1997).

    CAS  PubMed  Google Scholar 

  94. Sharma, S., Yang, J., Watzinger, P., Kötter, P. & Entian, K.D. Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively. Nucleic Acids Res. 41, 9062–9076 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Purta, E., O'Connor, M., Bujnicki, J.M. & Douthwaite, S. YccW is the m5C methyltransferase specific for 23S rRNA nucleotide 1962. J. Mol. Biol. 383, 641–651 (2008).

    CAS  PubMed  Google Scholar 

  96. Kimura, S. et al. Base methylations in the double-stranded RNA by a fused methyltransferase bearing unwinding activity. Nucleic Acids Res. 40, 4071–4085 (2012). Ref. 96 reports identification of the first rRNA-methyltransferase with two catalytic domains, each targeting a specific nucleotide.

    CAS  PubMed  Google Scholar 

  97. Lee, K.W. & Bogenhagen, D.F. Assignment of 2′-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16S ribosomal RNA (rRNA). J. Biol. Chem. 289, 24936–24942 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Sharma, S. et al. Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m3U methylations of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 42, 3246–3260 (2014).

    CAS  PubMed  Google Scholar 

  99. Lesnyak, D.V., Sergiev, P.V., Bogdanov, A.A. & Dontsova, O.A. Identification of Escherichia coli m2G methyltransferases: I. the ycbY gene encodes a methyltransferase specific for G2445 of the 23 S rRNA. J. Mol. Biol. 364, 20–25 (2006).

    CAS  PubMed  Google Scholar 

  100. Purta, E., O'Connor, M., Bujnicki, J.M. & Douthwaite, S. S. YgdE is the 2′-O-ribose methyltransferase RlmM specific for nucleotide C2498 in bacterial 23S rRNA. Mol. Microbiol. 72, 1147–1158 (2009).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank P. Moore, M. Gagnon, J. Brown, and M. Svetlov for critical reading of the manuscript and valuable suggestions. We also thank all members of the P.V.S. and Y.S.P. laboratories for discussions and critical feedback. This work was supported by Illinois State startup funds (to Y.S.P.); Russian Foundation for Basic Research (16-04-01100 to P.V.S.); Russian Science Foundation (14-14-00072 to P.V.S.); and Moscow University Development Program (PNR 5.13 to P.V.S.).

Author information

Authors and Affiliations

  1. Skolkovo Institute of Science and Technology, Skolkovo, Moscow Region, Russia

    Petr V Sergiev, Anastasia A Chugunova & Olga A Dontsova

  2. Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia

    Petr V Sergiev, Anastasia A Chugunova & Olga A Dontsova

  3. A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia

    Petr V Sergiev & Olga A Dontsova

  4. Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, Illinois, USA

    Nikolay A Aleksashin

  5. Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, USA

    Yury S Polikanov

  6. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA

    Yury S Polikanov

Authors
  1. Petr V Sergiev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolay A Aleksashin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anastasia A Chugunova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yury S Polikanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olga A Dontsova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Petr V Sergiev or Yury S Polikanov.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sergiev, P., Aleksashin, N., Chugunova, A. et al. Structural and evolutionary insights into ribosomal RNA methylation. Nat Chem Biol 14, 226–235 (2018). https://doi.org/10.1038/nchembio.2569

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.2569

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing