MicroRNAs: Key Modulators of Posttranscriptional Gene Expression

The temporal and spatial expression of proteins defines cell-specific activities and how a given cell responds to a local microenvironment. Thus, cells have evolved numerous integrated mechanisms to control which proteins are expressed and where they function at any given time. A small percentage of the human genome (<2%) encodes for messenger RNA (mRNA). A growing body of evidence suggests that noncoding RNAs (those that do not encode protein) constitute a substantial class of functional RNAs. Since the discovery that a small RNA molecule could control developmental transitions in Caenorhabditis elegans,1 microRNAs have been identified in numerous metazoans. In the past few years, human microRNAs (685 currently listed in the microRNA registry, version 11.0) have been shown to have a major role in complex gene regulatory networks and are estimated to contribute to the regulation of one third of all human genes. MicroRNAs, along with transcription factors, constitute the largest family of trans-acting, gene regulatory molecules, whose cell-specific expression directly and precisely regulate cellular functions. It is therefore not surprising that microRNAs are implicated in a wide variety of diseases, including cancer and diabetes mellitus. The role of microRNAs in the biology and pathobiology of GI tissues is now being unraveled. The purpose of this minireview is to provide current information on microRNA synthesis and processing, as well as microRNA-dependent gene regulation events that influence GI tissues in health and disease, and to highlight the potential of microRNAs for diagnosis and therapy.