Amino-acid-dependent shift in tRNA synthetase editing mechanisms

Journal of the American Chemical Society
Jaya Sarkar, Susan A Martinis


Many aminoacyl-tRNA synthetases prevent mistranslation by relying upon proofreading activities at multiple stages of the aminoacylation reaction. In leucyl-tRNA synthetase (LeuRS), editing activities that precede or are subsequent to tRNA charging have been identified. Although both are operational, either the pre- or post-transfer editing activity can predominate. Yeast cytoplasmic LeuRS (ycLeuRS) misactivates structurally similar noncognate amino acids including isoleucine and methionine. We show that ycLeuRS has a robust post-transfer editing activity that efficiently clears tRNA(Leu) mischarged with isoleucine. In comparison, the enzyme's post-transfer hydrolytic activity against tRNA(Leu) mischarged with methionine is weak. Rather, methionyl-adenylate is cleared robustly via an enzyme-mediated pre-transfer editing activity. We hypothesize that, similar to E. coli LeuRS, ycLeuRS has coexisting functional pre- and post-transfer editing activities. In the case of ycLeuRS, a shift between the two editing pathways is triggered by the identity of the noncognate amino acid.


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Related Concepts

LARS gene
Alkalescens-Dispar Group
Amino Acids, I.V. solution additive
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Amino Acyl-tRNA Synthetases
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