A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia.

Kuncha, Santosh Kumar; Mazeed, Mohd; Singh, Raghvendra; Kattula, Bhavita; Routh, Satya Brata; Sankaranarayanan, Rajan · Nat Commun · 2018

basic_science · Level V

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Abstract

D-aminoacyl-tRNA deacylase (DTD), a bacterial/eukaryotic trans-editing factor, removes D-amino acids mischarged on tRNAs and achiral glycine mischarged on tRNA<sup>Ala</sup>. An invariant cross-subunit Gly-cisPro motif forms the mechanistic basis of L-amino acid rejection from the catalytic site. Here, we present the identification of a DTD variant, named ATD (Animalia-specific tRNA deacylase), that harbors a Gly-transPro motif. The cis-to-trans switch causes a "gain of function" through L-chiral selectivity in ATD resulting in the clearing of L-alanine mischarged on tRNA<sup>Thr</sup>(G4•U69) by eukaryotic AlaRS. The proofreading activity of ATD is conserved across diverse classes of phylum Chordata. Animalia genomes enriched in tRNA<sup>Thr</sup>(G4•U69) genes are in strict association with the presence of ATD, underlining the mandatory requirement of a dedicated factor to proofread tRNA misaminoacylation. The study highlights the emergence of ATD during genome expansion as a key event associated with the evolution of Animalia.

Medical subject headings