tRNA modifications regulate translation during cellular stress
#MMPMID25304425
Gu C
; Begley TJ
; Dedon PC
FEBS Lett
2014[Nov]; 588
(23
): 4287-96
PMID25304425
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The regulation of gene expression in response to stress is an essential cellular
protection mechanism. Recent advances in tRNA modification analysis and
genome-based codon bias analytics have facilitated studies that lead to a novel
model for translational control, with translation elongation dynamically
regulated during stress responses. Stress-induced increases in specific anticodon
wobble bases are required for the optimal translation of stress response
transcripts that are significantly biased in the use of degenerate codons keyed
to these modified tRNA bases. These findings led us to introduce the notion of
tRNA modification tunable transcripts (MoTTs - transcripts whose translation is
regulated by tRNA modifications), which are identifiable using genome-wide codon
counting algorithms. In support of this general model of translational control of
stress response, studies making use of detailed measures of translation, tRNA
methyltransferase mutants, and computational and mass spectrometry approaches
reveal that stress reprograms tRNA modifications to translationally regulate
MoTTs linked to arginine and leucine codons, which helps cells survive insults by
damaging agents. These studies highlight how tRNA methyltransferase activities
and MoTTs are key components of the cellular stress response.
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