RNA-binding proteins implicated in the hypoxic response

Introduction Post-transcriptional gene regulation by hypoxia Control of mRNA turnover mRNA decay mRNA stabilization Control of translation Translational inhibition Translational activation HuR HIF-1 alpha mRNA VEGF mRNA GLUT1, p53, TGF-beta and c-myc mRNAs PTB HIF-1 alpha 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-1 alpha 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.