Talk abstracts

Talk on Saturday 11:45-12:00pm submitted by Oscar Vargas-Rodriguez

Divergent tRNA Recognition and Editing by the YbaK Superfamily

Oscar Vargas-Rodriguez (Chemistry and Biochemistry and Center for RNA Biology. The Ohio State University), Mom Das (Chemistry and Biochemistry and Center for RNA Biology. The Ohio State University), Karin Musier-Forsyth (Chemistry and Biochemistry and Center for RNA Biology. The Ohio State University)

Abstract:
Despite their high tRNA selectivity, many aminoacyl-tRNA synthetases mis-activate non-cognate amino acids that are structurally similar to their cognate substrate. For example, prolyl-tRNA synthetase (ProRS) fails to effectively discriminate between cognate Pro and non-cognate Ala and Cys. In most bacteria, mischarged Ala-tRNAPro is hydrolyzed in a catalytic domain distinct from the synthetic active site (INS). In contrast, Cys-tRNAPro, is cleared by YbaK, a single domain homolog of INS. Although most bacteria employ this “triple-sieve” editing mechanism, some bacterial species encode a ProRS that lacks the INS domain. Five distinct families of INS homologs collectively known as the YbaK superfamily have now been identified (YbaK, PrdX, ProX, PA2301, and YeaK), and alternative triple-sieve editing mechanisms exist. For example, Caulobacter crescentus (Cc) lacks a full-length INS domain and relies on the trans editing activities of both YbaK (Cys editing) and PrdX (Ala editing). In addition, YbaK, PrdX, and INS use divergent mechanisms to recognize their aa-tRNAPro substrates. PrdX recognizes the discriminator base (A73) and the first (C1:G72) base pair of tRNAPro, and also collaborates with elongation factor Tu to ensure hydrolysis of only Ala-tRNAPro and not Ala-tRNAAla. In contrast, INS and YbaK do not appear to recognize specific acceptor stem elements. Whereas the INS domain of ProRS depends on correct anticodon recognition to hydrolyze only Ala-tRNAPro, YbaK interacts with ProRS to ensure specific cleavage of Cys-tRNAPro and not Cys-tRNACys. Taken together, these data highlight the diversity of mechanisms used by the YbaK superfamily to maintain the fidelity of Pro codon translation.

Keywords: tRNA, aminoacyl-tRNA synthetases, editing