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Fig. 2 | Genome Biology

Fig. 2

From: Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses

Fig. 2

tRNA reprogramming and codon-biased translation of stress-response proteins. a Model illustrating the effects on Mycobacterium bovis BCG of hypoxia encountered during infection. Hypoxia induces expression of 48 proteins in the Dos regulon that causes the cell to become dormant. b The tRNA epitranscriptome consists of over 120 post-transcriptionally inserted modified ribonucleosides. During hypoxia, the relative quantities of 40 tRNA modifications (rows in heat map) change as a function of time during the response to the stress (days 0–21; columns in heat map) and again during O2 resuscitation (days 22–24). In early hypoxia (day 9), the wobble position of tRNAThrUGU, which reads the codon ACG, switches from 5-methoxyuridine (mo5U) to 5-oxyacetic acid uridine (cmo5U; structure shown). c RNase/LC-MS maps cmo5U to the wobble of tRNAThrUGU. d Families of response genes are organized by biased use of synonymous codons. The heat map shows over-use (purple) and under-use (yellow) of 62 codons (columns) across all genes (rows) in BCG. The gene for DosR, the master regulator of the 48-gene Dos regulon, over-uses the ACG codon and under-uses ACC, the most common Thr codon. e Codon analysis of proteomics data shows that > 80% of proteins upregulated in early hypoxia use ACG to code for Thr, whereas downregulated proteins are enriched in the so-called ‘optimal’ codon for Thr, ACC. Evidence that the auxiliary information in the genetic code is utilized for regulatory purposes is supported by examining codons associated with highly upregulated and downregulated proteins across all time-points of hypoxia in BCG. Pairs of synonymous codons are differentially enriched in upregulated and downregulated proteins, with the codon enrichments defining functional gene families. Alk phos alkaline phosphatase, PLS partial least squares, Thr threonine

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