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

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

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1National Center for Biotechnology Information; National Library of Medicine; National Institutes of Health; Bethesda, MD USA.


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.


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

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