MicroRNA Biogenesis in Hypoxia

Abstract

MicroRNAs (miRNAs) are 17-22 nucleotide, non-coding, single stranded RNA molecules that play a key role in post-transcriptional gene regulation. Hypoxia is a reduction in the normal level of tissue oxygen (O2) tension, and is a feature of chronic vascular disease, pulmonary disease and many cancers. Tissue hypoxia can have widespread effects on cellular functions, as O2 availability is critical for many cellular processes. Cells respond to changes in O2 tension through multiple molecular and cellular mechanisms, including changes in gene expression through transcriptional and translational mechanisms. The transcription factor, hypoxia inducible factor-1, plays a dominant role in transcriptional gene regulation in hypoxia. Several hypoxically induced miRNAs have been shown to play important roles in the hypoxic adaptation of cancer cells. Global repression of enzymes critical for miRNA biogenesis seems to be a widespread phenomenon with several different mechanisms operating. This review describes the effects of hypoxia on specific miRNAs and more global effects on miRNA biogenesis, demonstrating that hypoxia is an important regulator of miRNA biogenesis and function.

Keywords: Biogenesis; DICER; DROSHA; HIF; hypoxia; microRNA.