• Open Access

RNA-binding proteins implicated in the hypoxic response

Authors

  • Kiyoshi Masuda,

    1. Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
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  • Kotb Abdelmohsen,

    1. Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
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  • Myriam Gorospe

    Corresponding author
    1. Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
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*Correspondence to: Myriam GOROSPE, RNA Regulation Section, LCMB, NIA-IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Tel.: 410-558-8443
Fax: 410-558-8386
E-mail: myriam-gorospe@nih.gov

Abstract

  • • Introduction
  • • Post-transcriptional gene regulation by hypoxia
    • - Control of mRNA turnover
      • - mRNA decay
      • - mRNA stabilization
    • - Control of translation
      • - Translational inhibition
      • - Translational activation
  • • HuR
    • - HIF-1α mRNA
    • - VEGF mRNA
    • - GLUT1, p53, TGF-β and c-myc mRNAs
  • • PTB
    • - HIF-1α mRNA
    • - VEGF mRNA
    • - Insulin mRNA
  • • Other RBPs implicated in the response to hypoxia
    • - IRPs
    • - CPEBs
    • - hnRNPs
    • - TIA-1, TIAR and RBPs present in SGs
    • - ERBP
  • • Perspective

In cells responding to low oxygen levels, gene expression patterns are strongly influenced by post-transcriptional processes. RNA-binding proteins (RBPs) are pivotal regulators of gene expression in response to numerous stresses, including hypoxia. Here, we review the RBPs that modulate mRNA turnover and translation in response to hypoxic challenge. The RBPs HuR (human antigen R) and PTB (polypyrimidine tract-binding protein) associate with mRNAs encoding hypoxia-response proteins such as HIF-1α and VEGF mRNAs, enhance their expression after hypoxia and play a major role in establishing hypoxic gene expression patterns. Additional RBPs such as iron-response element-binding proteins (IRPs), cytoplasmic polyadenylation-element-binding proteins (CPEBs) and several heterogeneous nuclear ribonucleoproteins (hnRNPs) also bind to hypoxia-regulated transcripts and modulate the levels of the encoded proteins. We discuss the efficient regulation of hypoxic gene expression by RBPs and the mounting interest in targeting hypoxia-regulatory RBPs in diseases with aberrant hypoxic responses.

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