Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular
Kotb Abdelmohsen1, Yuki Kuwano, Hyeon Ho Kim
1Laboratory of Cellular and Molecular Biology, National Institute on Aging - Intramural Research Program, National Institutes of Health, Baltimore, MD 21228, USA.
Abstract:
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.
Insights
Mammalian cells use mRNA turnover and translation regulatory (TTR) proteins to manage oxidative stress. Changes in these TTR proteins with aging impair cellular responses to oxidative damage.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Mammalian cells activate complex gene expression programs to counteract oxidative stress.
- Posttranscriptional mechanisms, including mRNA turnover and translation, are crucial for oxidant-triggered gene expression.
- mRNA-binding proteins (RBPs) play a significant role in regulating these processes.
Purpose of the Study:
- To review recent advancements in understanding turnover and translation regulatory (TTR) mRNA-binding proteins (RBPs).
- To explore how TTR-RBPs influence gene expression in response to oxidative damage.
- To examine the role of TTR-RBPs in cellular senescence and aging.
Main Methods:
- Identification of oxidant damage-regulated mRNAs targeted by TTR-RBPs.
- Review of signaling pathways that control TTR-RBP function under oxidative stress.
- Examination of evidence linking TTR-RBP activity alterations to senescence and aging.
Main Results:
- Specific mRNAs regulated by oxidative damage and TTR-RBPs have been identified.
- Oxidant-triggered signaling pathways governing TTR-RBP function are elucidated.
- Evidence suggests TTR-RBP activity is altered in senescent cells and with advancing age.
Conclusions:
- TTR-RBPs are key regulators of gene expression in response to oxidative stress.
- Senescence-associated alterations in TTR-RBPs contribute to diminished cellular defense against oxidative damage.
- Dysregulation of TTR-RBPs may underlie age-related decline in cellular resilience.
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