A highly conserved family of domains related to the DNA-glycosylase fold helps predict multiple novel pathways for RNA modifications

RNA Biol. 2014;11(4):360-72. doi: 10.4161/rna.28302. Epub 2014 Mar 5.

Abstract

A protein family including mammalian NEMF, Drosophila caliban, yeast Tae2, and bacterial FpbA-like proteins was first defined over a decade ago and found to be universally distributed across the three domains/superkingdoms of life. Since its initial characterization, this family of proteins has been tantalizingly linked to a wide range of biochemical functions. Tapping the enormous wealth of genome information that has accumulated since the initial characterization of these proteins, we perform a detailed computational analysis of the family, identifying multiple conserved domains. Domains identified include an enzymatic domain related to the formamidopyrimidine (Fpg), MutM, and Nei/EndoVIII family of DNA glycosylases, a novel, predicted RNA-binding domain, and a domain potentially mediating protein-protein interactions. Through this characterization, we predict that the DNA glycosylase-like domain catalytically operates on double-stranded RNA, as part of a hitherto unknown base modification mechanism that probably targets rRNAs. At least in archaea, and possibly eukaryotes, this pathway might additionally include the AMMECR1 family of proteins. The predicted RNA-binding domain associated with this family is also observed in distinct architectural contexts in other proteins across phylogenetically diverse prokaryotes. Here it is predicted to play a key role in a new pathway for tRNA 4-thiouridylation along with TusA-like sulfur transfer proteins.

Keywords: DNA glycosylase; FbpA; IscS; NEMF; Tae2; TusA; base modification; caliban; fibronectin-binding; tRNA 4-thiouridylation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Computational Biology
  • Conserved Sequence
  • DNA Glycosylases / chemistry*
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • Protein Conformation
  • Protein Folding*
  • Protein Interaction Domains and Motifs* / genetics
  • RNA / chemistry
  • RNA / metabolism*
  • Sequence Alignment

Substances

  • RNA
  • DNA Glycosylases