microRNA mechanism and its involvement in DNA damage response pathway

Martin Bushell1

1MRC Toxicology Unit, Leicester, UK

Abstract

The discovery of microRNAs (miRNAs) has revolutionised the way in which we view gene expression. In human`s there are approximately 1000 miRNAs in the genome, each on average targeting ~200 different mRNAs, with estimates suggesting that at least 60% of all protein encoding mRNAs are controlled by miRNAs. Intensive analysis of tissues from a large diverse set of human diseases has shown dramatic alterations in the miRNAs profiles following disease onset. Moreover, global changes in miRNA function either by, alterations in the miRNA biogenesis pathways or changes in the target mRNA's 3'UTR length have been observed in many disease setting. Regardless of the disregulation mechanisms, miRNAs have been shown to be sufficient and required for the development of a number of diseases, particularly cancer. These small non-coding RNA molecules inhibit gene expression by binding to complementary regions within target mRNAs. It is well known that following engagement with the target mRNA, miRNAs induce both the translation repression and cause mRNA destabilisation of the targeted mRNA. However, the exact mechanism by which these small RNA molecules control gene expression has remained elusive. Here I will discuss our investigations into how miRNAs control gene expression and show how the miRNA biogenesis enzymes appear to have a second pivotal cellular function, moonlighting in the DNA repair pathway.