Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms13302
Title: TRNA-mediated codon-biased translation in mycobacterial hypoxic persistence
Authors: Chionh, Y.H
McBee, M
Babu, I.R
Hia, F
Lin, W 
Zhao, W
Cao, J
Dziergowska, A
Malkiewicz, A
Begley, T.J
Alonso, S 
Dedon, P.C
Keywords: heat shock protein
messenger RNA
ribonucleoside
transfer RNA
bacterial protein
bacterial RNA
transcriptome
transfer RNA
amino acid
bacterium
gene expression
hypoxia
molecular analysis
pathogen
protein
RNA
tuberculosis
Article
bacterial survival
bacteriostasis
cell reprogramming technique
codon
codon usage
environmental change
gene expression
granuloma
hypoxia
Mycobacterium bovis BCG
nonhuman
RNA translation
gene expression regulation
genetics
metabolism
Mycobacterium bovis
oxygen consumption
physiology
protein processing
protein synthesis
Bacteria (microorganisms)
Corynebacterineae
Mycobacterium bovis BCG
Bacterial Proteins
Codon
Gene Expression Regulation, Bacterial
Mycobacterium bovis
Oxygen Consumption
Protein Biosynthesis
Protein Processing, Post-Translational
RNA, Bacterial
RNA, Messenger
RNA, Transfer
Transcriptome
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Chionh, Y.H, McBee, M, Babu, I.R, Hia, F, Lin, W, Zhao, W, Cao, J, Dziergowska, A, Malkiewicz, A, Begley, T.J, Alonso, S, Dedon, P.C (2016). TRNA-mediated codon-biased translation in mycobacterial hypoxic persistence. Nature Communications 7 : 13302. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms13302
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 cmo5U in tRNAThr(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. © The Author(s) 2016.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/174918
ISSN: 20411723
DOI: 10.1038/ncomms13302
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