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. 1999 Aug 1;27(15):3138–3145. doi: 10.1093/nar/27.15.3138

Exposition of a family of RNA m(5)C methyltransferases from searching genomic and proteomic sequences.

R Reid 1, P J Greene 1, D V Santi 1
PMCID: PMC148540  PMID: 10454610

Abstract

The Escherichia coli fmu gene product has recently been determined to be the 16S rRNA m(5)C 967 methyltransferase. As such, Fmu represents the first protein identified as an S -adenosyl-L-methionine (AdoMet)- dependent RNA m(5)C methyltransferase whose amino acid sequence is known. Using the amino acid sequence of Fmu as an initial probe in an iterative search of completed DNA sequence databases, 27 homologous ORF products were identified as probable RNA m(5)C methyltransferases. Further analysis of sequences in undeposited genomic sequencing data and EST databases yielded more than 30 additional homologs. These putative RNA m(5)C methyltransferases are grouped into eight subfamilies, some of which are predicted to consist of direct genetic counterparts, or orthologs. The enzymes proposed to be RNA m(5)C methyltransferases have sequence motifs closely related to signature sequences found in the well-studied DNA m(5)C methyltransferases and other AdoMet-dependent methyltransferases. Structure-function correlates in the known AdoMet methyltransferases support the assignment of this family as RNA m(5)C methyltransferases.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bakin A., Ofengand J. Mapping of the 13 pseudouridine residues in Saccharomyces cerevisiae small subunit ribosomal RNA to nucleotide resolution. Nucleic Acids Res. 1995 Aug 25;23(16):3290–3294. doi: 10.1093/nar/23.16.3290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brimacombe R. The structure of ribosomal RNA: a three-dimensional jigsaw puzzle. Eur J Biochem. 1995 Jun 1;230(2):365–383. [PubMed] [Google Scholar]
  4. Busch H., Busch R. K., Freeman J. W., Perlaky L. Nucleolar protein P120 and its targeting for cancer chemotherapy. Boll Soc Ital Biol Sper. 1991 Aug;67(8):739–750. [PubMed] [Google Scholar]
  5. Bussiere D. E., Muchmore S. W., Dealwis C. G., Schluckebier G., Nienaber V. L., Edalji R. P., Walter K. A., Ladror U. S., Holzman T. F., Abad-Zapatero C. Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic resistance in bacteria. Biochemistry. 1998 May 19;37(20):7103–7112. doi: 10.1021/bi973113c. [DOI] [PubMed] [Google Scholar]
  6. Cheng X. DNA modification by methyltransferases. Curr Opin Struct Biol. 1995 Feb;5(1):4–10. doi: 10.1016/0959-440x(95)80003-j. [DOI] [PubMed] [Google Scholar]
  7. Cheng X., Kumar S., Posfai J., Pflugrath J. W., Roberts R. J. Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine. Cell. 1993 Jul 30;74(2):299–307. doi: 10.1016/0092-8674(93)90421-l. [DOI] [PubMed] [Google Scholar]
  8. Cheng X. Structure and function of DNA methyltransferases. Annu Rev Biophys Biomol Struct. 1995;24:293–318. doi: 10.1146/annurev.bb.24.060195.001453. [DOI] [PubMed] [Google Scholar]
  9. Eady E. A., Ross J. I., Cove J. H. Multiple mechanisms of erythromycin resistance. J Antimicrob Chemother. 1990 Oct;26(4):461–465. doi: 10.1093/jac/26.4.461. [DOI] [PubMed] [Google Scholar]
  10. Fonagy A., Swiderski C., Dunn M., Freeman J. W. Antisense-mediated specific inhibition of P120 protein expression prevents G1- to S-phase transition. Cancer Res. 1992 Oct 1;52(19):5250–5256. [PubMed] [Google Scholar]
  11. Fonagy A., Swiderski C., Wilson A., Bolton W., Kenyon N., Freeman J. W. Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts. J Cell Physiol. 1993 Jan;154(1):16–27. doi: 10.1002/jcp.1041540104. [DOI] [PubMed] [Google Scholar]
  12. Freeman J. W., McGrath P., Bondada V., Selliah N., Ownby H., Maloney T., Busch R. K., Busch H. Prognostic significance of proliferation associated nucleolar antigen P120 in human breast carcinoma. Cancer Res. 1991 Apr 15;51(8):1973–1978. [PubMed] [Google Scholar]
  13. Gong W., O'Gara M., Blumenthal R. M., Cheng X. Structure of pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment. Nucleic Acids Res. 1997 Jul 15;25(14):2702–2715. doi: 10.1093/nar/25.14.2702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gu X. R., Gustafsson C., Ku J., Yu M., Santi D. V. Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli. Biochemistry. 1999 Mar 30;38(13):4053–4057. doi: 10.1021/bi982364y. [DOI] [PubMed] [Google Scholar]
  15. Hong B., Brockenbrough J. S., Wu P., Aris J. P. Nop2p is required for pre-rRNA processing and 60S ribosome subunit synthesis in yeast. Mol Cell Biol. 1997 Jan;17(1):378–388. doi: 10.1128/mcb.17.1.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. King M., Ton D., Redman K. L. A conserved motif in the yeast nucleolar protein Nop2p contains an essential cysteine residue. Biochem J. 1999 Jan 1;337(Pt 1):29–35. [PMC free article] [PubMed] [Google Scholar]
  17. Klimasauskas S., Kumar S., Roberts R. J., Cheng X. HhaI methyltransferase flips its target base out of the DNA helix. Cell. 1994 Jan 28;76(2):357–369. doi: 10.1016/0092-8674(94)90342-5. [DOI] [PubMed] [Google Scholar]
  18. Koonin E. V. Prediction of an rRNA methyltransferase domain in human tumor-specific nucleolar protein P120. Nucleic Acids Res. 1994 Jul 11;22(13):2476–2478. doi: 10.1093/nar/22.13.2476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kumar S., Cheng X., Klimasauskas S., Mi S., Posfai J., Roberts R. J., Wilson G. G. The DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 1994 Jan 11;22(1):1–10. doi: 10.1093/nar/22.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maden B. E. The numerous modified nucleotides in eukaryotic ribosomal RNA. Prog Nucleic Acid Res Mol Biol. 1990;39:241–303. doi: 10.1016/s0079-6603(08)60629-7. [DOI] [PubMed] [Google Scholar]
  21. Malone T., Blumenthal R. M., Cheng X. Structure-guided analysis reveals nine sequence motifs conserved among DNA amino-methyltransferases, and suggests a catalytic mechanism for these enzymes. J Mol Biol. 1995 Nov 3;253(4):618–632. doi: 10.1006/jmbi.1995.0577. [DOI] [PubMed] [Google Scholar]
  22. O'Gara M., Klimasauskas S., Roberts R. J., Cheng X. Enzymatic C5-cytosine methylation of DNA: mechanistic implications of new crystal structures for HhaL methyltransferase-DNA-AdoHcy complexes. J Mol Biol. 1996 Sep 6;261(5):634–645. doi: 10.1006/jmbi.1996.0489. [DOI] [PubMed] [Google Scholar]
  23. O'Gara M., Roberts R. J., Cheng X. A structural basis for the preferential binding of hemimethylated DNA by HhaI DNA methyltransferase. J Mol Biol. 1996 Nov 8;263(4):597–606. doi: 10.1006/jmbi.1996.0601. [DOI] [PubMed] [Google Scholar]
  24. Pues H., Bleimling N., Holz B., Wölcke J., Weinhold E. Functional roles of the conserved aromatic amino acid residues at position 108 (motif IV) and position 196 (motif VIII) in base flipping and catalysis by the N6-adenine DNA methyltransferase from Thermus aquaticus. Biochemistry. 1999 Feb 2;38(5):1426–1434. doi: 10.1021/bi9818016. [DOI] [PubMed] [Google Scholar]
  25. Pósfai J., Bhagwat A. S., Pósfai G., Roberts R. J. Predictive motifs derived from cytosine methyltransferases. Nucleic Acids Res. 1989 Apr 11;17(7):2421–2435. doi: 10.1093/nar/17.7.2421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pósfai J., Bhagwat A. S., Roberts R. J. Sequence motifs specific for cytosine methyltransferases. Gene. 1988 Dec 25;74(1):261–265. doi: 10.1016/0378-1119(88)90299-5. [DOI] [PubMed] [Google Scholar]
  27. Schluckebier G., O'Gara M., Saenger W., Cheng X. Universal catalytic domain structure of AdoMet-dependent methyltransferases. J Mol Biol. 1995 Mar 17;247(1):16–20. doi: 10.1006/jmbi.1994.0117. [DOI] [PubMed] [Google Scholar]
  28. Smith J. E., Cooperman B. S., Mitchell P. Methylation sites in Escherichia coli ribosomal RNA: localization and identification of four new sites of methylation in 23S rRNA. Biochemistry. 1992 Nov 10;31(44):10825–10834. doi: 10.1021/bi00159a025. [DOI] [PubMed] [Google Scholar]
  29. Tscherne J. S., Nurse K., Popienick P., Michel H., Sochacki M., Ofengand J. Purification, cloning, and characterization of the 16S RNA m5C967 methyltransferase from Escherichia coli. Biochemistry. 1999 Feb 9;38(6):1884–1892. doi: 10.1021/bi981880l. [DOI] [PubMed] [Google Scholar]
  30. Valdez B. C., Perlaky L., Henning D., Saijo Y., Chan P. K., Busch H. Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein B23. J Biol Chem. 1994 Sep 23;269(38):23776–23783. [PubMed] [Google Scholar]
  31. Wu J. C., Santi D. V. Kinetic and catalytic mechanism of HhaI methyltransferase. J Biol Chem. 1987 Apr 5;262(10):4778–4786. [PubMed] [Google Scholar]
  32. Wu P., Brockenbrough J. S., Paddy M. R., Aris J. P. NCL1, a novel gene for a non-essential nuclear protein in Saccharomyces cerevisiae. Gene. 1998 Oct 5;220(1-2):109–117. doi: 10.1016/s0378-1119(98)00330-8. [DOI] [PubMed] [Google Scholar]
  33. Xu S., Xiao J., Posfai J., Maunus R., Benner J., 2nd Cloning of the BssHII restriction-modification system in Escherichia coli : BssHII methyltransferase contains circularly permuted cytosine-5 methyltransferase motifs. Nucleic Acids Res. 1997 Oct 15;25(20):3991–3994. doi: 10.1093/nar/25.20.3991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yu L., Petros A. M., Schnuchel A., Zhong P., Severin J. M., Walter K., Holzman T. F., Fesik S. W. Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance. Nat Struct Biol. 1997 Jun;4(6):483–489. doi: 10.1038/nsb0697-483. [DOI] [PubMed] [Google Scholar]

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