tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27834374.
- Also identified by DOI 10.1038/ncomms13302 and PMC identifier 5114619.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria-which models tuberculous granulomas-are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo<sup>5</sup>U in tRNA<sup>Thr(UGU)</sup>, which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria.
Medical subject headings
- Bacterial Proteins
- Codon
- Gene Expression Regulation, Bacterial
- Mycobacterium bovis
- Protein Processing, Post-Translational
- RNA, Transfer