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Journal of Molecular Evolution

, Volume 55, Issue 4, pp 431–444 | Cite as

Structure Prediction and Phylogenetic Analysis of a Functionally Diverse Family of Proteins Homologous to the MT-A70 Subunit of the Human mRNA:m6A Methyltransferase

  • Janusz M. Bujnicki
  • Marcin  Feder
  • Monika  Radlinska
  • Robert M. Blumenthal

MT-A70 is the S-adenosylmethionine-binding subunit of human mRNA:m6A methyl-transferase (MTase), an enzyme that sequence-specifically methylates adenines in pre-mRNAs. The physiological importance yet limited understanding of MT-A70 and its apparent lack of similarity to other known RNA MTases combined to make this protein an attractive target for bioinformatic analysis. The sequence of MT-A70 was subjected to extensive in silico analysis to identify orthologous and paralogous polypeptides. This analysis revealed that the MT-A70 family comprises four subfamilies with varying degrees of interrelatedness. One subfamily is a small group of bacterial DNA:m6A MTases. The other three subfamilies are paralogous eukaryotic lineages, two of which have not been associated with MTase activity but include proteins having substantial regulatory effects. Multiple sequence alignments and structure prediction for members of all four subfamilies indicated a high probability that a consensus MTase fold domain is present. Significantly, this consensus fold shows the permuted topology characteristic of the b class of MTases, which to date has only been known to include DNA MTases.

Keywords

Polypeptide Adenine Multiple Sequence Alignment Bioinformatic Analysis Structure Prediction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag New York Inc. 2002

Authors and Affiliations

  • Janusz M. Bujnicki
    • 1
  • Marcin  Feder
    • 1
  • Monika  Radlinska
    • 2
  • Robert M. Blumenthal
    • 3
  1. 1.Bioinformatics Laboratory, International Institute of Molecular and Cell Biology, ul. ks. Trojdena 4, 02-109 Warsaw, PolandPL
  2. 2.Institute of Microbiology, Warsaw University, ul. Miecznikowa 1, 02-093 Warsaw, PolandPL
  3. 3.Department of Microbiology & Immunology and Program in Bioinformatics & Proteomics/Genomics, Medical College of Ohio, 3055 Arlington Avenue, Toledo, OH 43614-5806, USAUS

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