tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence
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.; Alonso, Sylvie; Dedon, Peter C.; ... Show more Show less
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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.
DepartmentMassachusetts 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
Nature Publishing Group
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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