title: A highly conserved family of domains related to the DNA-glycosylase fold helps predict multiple novel pathways for RNA modifications.
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.
authors.affiliation: 1National Center for Biotechnology Information; National Library of Medicine; National Institutes of Health; Bethesda, MD USA.
authors.forename: A Maxwell
authors.initials: AM
authors.lastname: Burroughs
authors.affiliation: 1National Center for Biotechnology Information; National Library of Medicine; National Institutes of Health; Bethesda, MD USA.
authors.forename: L
authors.initials: L
authors.lastname: Aravind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D017124:Conserved Sequence; D045647:DNA Glycosylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D012313:RNA; D045647:DNA Glycosylases
keywords: DNA glycosylase; FbpA; IscS; NEMF; Tae2; TusA; base modification; caliban; fibronectin-binding; tRNA 4-thiouridylation