Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence

Biol Chem. 2008 Mar;389(3):243-55. doi: 10.1515/BC.2008.022.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antigens, Surface / physiology
  • Cellular Senescence / physiology*
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Gene Expression Regulation / physiology*
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / physiology
  • Humans
  • Interleukin-1beta / physiology
  • Interleukin-2 / physiology
  • Interleukin-8 / physiology
  • Nuclear Factor 90 Proteins / physiology
  • Oxidative Stress / physiology*
  • Protein Kinases / physiology
  • RNA Processing, Post-Transcriptional / physiology*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / physiology*
  • Reactive Oxygen Species / metabolism
  • TATA-Binding Protein Associated Factors / physiology
  • Trans-Activators / physiology
  • Tristetraprolin / physiology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Antigens, Surface
  • BRF1 protein, human
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • HNRPD protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Hnrpd protein, mouse
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-8
  • KSRP protein, mouse
  • Nuclear Factor 90 Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • TATA-Binding Protein Associated Factors
  • Trans-Activators
  • Tristetraprolin
  • Tumor Necrosis Factor-alpha
  • ZFP36 protein, human
  • TIAL1 protein, human
  • Protein Kinases