Micro-RNA mediated regulation of proliferation, self-renewal and differentiation of mammalian stem cells

Abstract

Metazoan growth and development is maintained by populations of undifferentiated cells, commonly known as stem cells. Stem cells possess several characteristic properties, including dividing through self-renewing divisions and generating progeny that differentiate to have specialized cell fates. Multiple signaling pathways have been identified which coordinate stem cell proliferation with maintenance and differentiation. Relatively recently, the small, non-protein coding microRNAs (miRNAs) have been identified to function as important regulators in stem cell development. Individual miRNAs are capable of directing the translational repression of many mRNAs targets, generating widespread changes in gene expression. In addition, dysfunction of miRNA expression is commonly associated with cancer development. Cancer stem cells, which are likely responsible for initiating and maintaining tumorigenesis, share many similarities with stem cells and some mechanisms of miRNA function may be in common between these two cell types.

Figure 1

miRNA biogenesis and activity. miRNAs are transcribed from multiple genomic loci and processed by two cleavage steps to generate a mature 19–25 nucleotide long RNA fragment. Mature miRNAs direct the RISC complex to target mRNAs, resulting in either an upregulation of translation, but more commonly mRNA degradation and translational inhibition. See text for more details.