tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence
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Author(s)
Chionh, Yok Hian
McBee, Megan
Babu, I. Ramesh
Hia, Fabian
Lin, Wenwei
Zhao, Wei
Cao, Jianshu
Dziergowska, Agnieszka
Malkiewicz, Andrzej
Begley, Thomas J.
Date Issued
November 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Chionh, Yok Hian, Megan McBee, I. Ramesh Babu, Fabian Hia, Wenwei Lin, Wei Zhao, Jianshu Cao, et al. “tRNA-Mediated Codon-Biased Translation in Mycobacterial Hypoxic Persistence.” Nature Communications 7 (November 11, 2016): 13302. © 2016 Macmillan Publishers Limited
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Final published version
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[superscript 5]U in tRNA[superscript Thr(UGU)], 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.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
Singapore-MIT Alliance in Research and Technology (SMART)
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DOI of Published Version
https://doi.org/10.1038/ncomms13302
