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.

Biological Chemistry
|January 8, 2008
PubMed

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.

Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...