Defects in transient tRNA translocation bypass tRNA synthetase quality control mechanisms

Rachel A. Hellmann, Susan A. Martinis

Research output: Contribution to journalArticlepeer-review

Abstract

Quality control mechanisms during protein synthesis are essential to fidelity and cell survival. Leucyl-tRNA synthetase (LeuRS) misactivates non-leucine amino acids including isoleucine, methionine, and norvaline. To prevent translational errors, mischarged tRNA products are translocated 30 Å from the canonical aminoacylation core to a hydrolytic editing-active site within a completely separate domain. Because it is transient, the tRNA translocation mechanism has been difficult to isolate. We have identified a "translocation peptide" within Escherichia coli LeuRS. Mutations in the translocation peptide cause tRNA to selectively bypass the editing-active site, resulting in mischarging that is lethal to the cell. This bypass mechanism also rescues aminoacylation of an editing site mutation that hydrolyzes correctly charged Leu-tRNALeu. Thus, these LeuRS mutants charge tRNALeu but fail to translocate these products to the hydrolytic site, where they are cleared to guard against genetic code ambiguities.

Original languageEnglish (US)
Pages (from-to)11478-11484
Number of pages7
JournalJournal of Biological Chemistry
Volume284
Issue number17
DOIs
StatePublished - Apr 24 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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