Amino-acid-dependent shift in tRNA synthetase editing mechanisms.
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.
Department of Biochemistry, University of Illinois at Urbana-Champaign, 419 Roger Adams Laboratory, Box B-4, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Jaya
J
Sarkar
Susan A
SA
Martinis
D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D012356:RNA, Transfer, Leu; D015003:Yeasts / Q000201:enzymology
D000596:Amino Acids; D012356:RNA, Transfer, Leu; D000604:Amino Acyl-tRNA Synthetases