Journal
GENES & DEVELOPMENT
Volume 31, Issue 13, Pages 1382-1395Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.302547.117
Keywords
mismatch repair; noncoding small RNA; RNA chaperone; ARN motif; adaptive mutagenesis
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Funding
- Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research
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Mismatch repair (MMR) is a conserved mechanism exploited by cells to correct DNA replication errors both in growing cells and under nongrowing conditions. Hfq (host factor for RNA bacteriophage Q beta replication), a bacterial Lsm family RNA-binding protein, chaperones RNA-RNA interactions between regulatory small RNAs (sRNAs) and target messenger RNAs (mRNAs), leading to alterations of mRNA translation and/or stability. Hfq has been reported to post-transcriptionally repress the DNA MMR gene mutS in stationary phase, possibly limiting MMR to allow increased mutagenesis. Here we report that Hfq deploys dual mechanisms to control mutS expression. First, Hfq binds directly to an (AAN)(3) motif within the mutS 5' untranslated region (UTR), repressing translation in the absence of sRNA partners both in vivo and in vitro. Second, Hfq acts in a canonical pathway, promoting base-pairing of ArcZ sRNA with the mutS leader to inhibit translation. Most importantly, using pathway-specific mutS chromosomal alleles that specifically abrogate either regulatory pathway or both, we demonstrate that tight control of MutS levels in stationary phase contributes to stress-induced mutagenesis. By interacting with the mutS leader, Hfq serves as a critical switch that modulates bacteria from high-fidelity DNA replication to stress-induced mutagenesis.
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