Regulation of microRNA function in somatic stem cell proliferation and differentiation

MicroRNAs (miRNAs) constitute an essential part of the gene networks that drive proliferation, viability and differentiation of stem and progenitor cells across different somatic lineages.Upstream of miRNAs is a network of cell type-specific transcription factors that function together with epigenetic regulators to tightly regulate miRNA levels spatially and temporally. miRNA levels are further fine-tuned through post-transcriptional mechanisms regulating their processing to the mature form as well as their stability.Downstream of miRNAs are large networks of mRNA targets that influence cell fate choice. Through suppression of these targets, the miRNAs can silence previously active or alternative gene programmes during cell fate transitions.The impact of any one miRNA on a particular mRNA target is influenced by multiple factors, including the number of available target sites within the mRNA, targeting of the mRNA simultaneously by other miRNAs and competition between targets for the same miRNA.Availability of and affinity to miRNA target sites within mRNAs is influenced by factors such as alternative splicing, alternative polyadenylation and RNA-binding protein synergism or antagonism to miRNA binding.