Journal
BIOLOGICAL CHEMISTRY
Volume 389, Issue 3, Pages 243-255Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/BC.2008.022
Keywords
mRNA stability; posttranscriptional gene regulation; reactive oxygen species (ROS) signaling pathway; RNA-binding proteins; translational control
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Funding
- NATIONAL INSTITUTE ON AGING [Z01AG000518, Z01AG000393, ZIAAG000518, ZIAAG000393] Funding Source: NIH RePORTER
- Intramural NIH HHS [Z01 AG000393] Funding Source: Medline
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To respond adequately to oxidative stress, mammalian cells elicit rapid and tightly controlled changes in gene expression patterns. Besides alterations in the subsets of transcribed genes, two posttranscriptional processes prominently influence the oxidant-triggered gene expression programs: mRNA turnover and translation. Here, we review recent progress in our knowledge of the turnover and translation regulatory (TTR) mRNA-binding proteins (RBPs) that influence gene expression in response to oxidative damage. Specifically, we identify oxidant damage-regulated mRNAs that are targets of TTR-RBPs, we review the oxidant-triggered signaling pathways that govern TTR-RBP function, and we examine emerging evidence that TTR-RBP activity is altered with senescence and aging. Given the potent influence of TTR-RBPs upon oxidant-regulated gene expression profiles, we propose that the senescence-associated changes in TTR-RBPs directly contribute to the impaired responses to oxidant damage that characterize cellular senescence and advancing age.
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