Mammalian gene expression patterns change profoundly in response to low
oxygen levels. These changes in gene expression programs are strongly influenced by post-transcriptional mechanisms mediated by
mRNA-binding factors:
RNA-binding proteins (RBPs) and
microRNAs (
miRNAs). Here, we review the RBPs and
miRNAs that modulate
mRNA turnover and translation in response to hypoxic challenge. RBPs such as HuR (human
antigen R), PTB (
polypyrimidine tract-binding protein),
heterogeneous nuclear ribonucleoproteins (hnRNPs),
tristetraprolin,
nucleolin,
iron-response element-
binding proteins (IRPs), and cytoplasmic polyadenylation-
element-
binding proteins (CPEBs), selectively bind to numerous
hypoxia-regulated transcripts and play a major role in establishing hypoxic gene expression patterns.
MiRNAs including miR-210, miR-373, and miR-21 associate with
hypoxia-regulated transcripts and further modulate the levels of the encoded
proteins to implement the hypoxic gene expression profile. We discuss the potent regulation of hypoxic gene expression by RBPs and
miRNAs and their integrated actions in the cellular hypoxic response.