Translation quality control is critical for bacterial responses to amino acid stress

Abstract

Gene expression relies on quality control for accurate transmission of genetic information. One mechanism that prevents amino acid misincorporation errors during translation is editing of misacylated tRNAs by aminoacyl-tRNA synthetases. In the absence of editing, growth is limited upon exposure to excess noncognate amino acid substrates and other stresses, but whether these physiological effects result solely from mistranslation remains unclear. To explore if translation quality control influences cellular processes other than protein synthesis, an Escherichia coli strain defective in Tyr-tRNA Phe editing was used. In the absence of editing, cellular levels of aminoacylated tRNA Phe were elevated during amino acid stress, whereas in the wild-type strain these levels declined under the same growth conditions. In the editing-defective strain, increased levels of aminoacylated tRNA Phe led to continued synthesis of the PheL leader peptide and attenuation of pheA transcription under amino acid stress. Consequently, in the absence of editing, activation of the phenylalanine biosynthetic operon becomes less responsive to phenylalanine limitation. In addition to raising aminoacylated tRNA levels, the absence of editing lowered the amount of deacylated tRNA Phe in the cell. This reduction in deacylated tRNA was accompanied by decreased synthesis of the second messenger guanosine tetraphosphate and limited induction of stringent response-dependent gene expression in editing-defective cells during amino acid stress. These data show that a single qualitycontrol mechanism, the editing of misacylated aminoacyl-tRNAs, provides a critical checkpoint both for maintaining the accuracy of translation and for determining the sensitivity of transcriptional responses to amino acid stress.translation | quality control | stress | stringent response

Evolution of Transcription Activator-Like Effectors in Xanthomonas oryzae

“…Selective pressure might also stem from differing accuracy of tRNAs with respect to loading with AAs and recognition accuracy of anticodons (Zhang et al 2015; Bullwinkle and Ibba 2016), but no data on the accuracy aminoacyl tRNA synthetases in Xanthomonas are currently available.…”

Function and origin of mistranslation in distinct cellular contexts

“…Removing the editing domain from the isoleucine-tRNA synthetase in bacteria can increase the growth rate during isoleucine limitation despite being deleterious to growth under most conditions (Pezo et al , 2004, Bacher et al , 2005, Bacher et al , 2007). Relatedly, mistranslation engendered through editing defects in PheRS in E. coli has also been shown to increase tolerance to specific types of amino acid stress (Bullwinkle and Ibba, 2016). These results demonstrate that certain types of mistranslation can be beneficial in very specific contexts.…”

Rewiring protein synthesis: From natural to synthetic amino acids

“…Editing defects in aaRS further increase DNA mutations in bacteria [95] and activates DNA damage response in zebrafish [96]. Recent work also suggests that a PheRS editing defect suppresses stringent response in E. coli [97], and a ribosomal error-prone mutation suppresses bacterial motility [98]. …”