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Publication Abstract from PubMed

Fidelity of translation, which is predominately dictated by the accuracy of aminoacyl-tRNA synthetases in pairing amino acids with correct tRNAs, is of central importance in biology. Yet, deliberate modifications of translational fidelity can be beneficial. Here we found human and not E. coli AlaRS has an intrinsic capacity for mis-pairing alanine onto non-alanyl-tRNAs including tRNACys. Consistently, a cysteine-to-alanine substitution was found in a reporter protein expressed in human cells. All human AlaRS-mischarged tRNAs have a G4:U69 base pair in the acceptor stem. The base pair is required for the mischarging. By solving the crystal structure of human AlaRS and comparing it to that of E. coli AlaRS, we identified a key sequence divergence between eukaryotes and bacteria that influences mischarging. Thus, the expanded tRNA specificity of AlaRS appears to be an evolutionary gain-of-function to provide posttranscriptional alanine substitutions in eukaryotic proteins for potential regulations.

Evolutionary gain of alanine mischarging to non-cognate tRNAs with a G4:U69 base pair.,Sun L, Gomes AC, He W, Zhou H, Wang X, Pan DW, Schimmel P, Pan T, Yang XL J Am Chem Soc. 2016 Sep 13. PMID:27622773^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.