Characterization of macromolecular complexes regulating let-7 microRNA biogenesis

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Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product, either a protein or an RNA. The regulation of gene expression is a phenomenon by which the genetic code is interpreted to give rise to the properties of cells, organs and organisms. Several recent discoveries have led to the idea that RNA is a key regulator of gene expression. In particular, a specific type of recently discovered RNAs, termed microRNAs, are now viewed as one of the largest groups of molecules that regulate gene expression in multi-cellular organisms. In humans, the levels of these microRNAs in cells are highly regulated to allow for proper development, and dysregulation of cellular levels of microRNAs is linked to several diseases, including cancer and neurological diseases. It is now clear that the levels of several microRNAs are regulated during their formation, which is usually referred to as their biogenesis. However, much remains to be known about the details of this regulation that occur during microRNA biogenesis. The long-term objective of our research program is to gain a fundamental understanding of specific regulatory mechanism that control the biogenesis of microRNAs. Our current focus is on the let-7 family of microRNAs, which were among the first microRNAs to be identified. The let-7 microRNAs play a central role in normal growth in humans and can block the development of cancer. It is well known that the biogenesis of microRNAs from the let-7 family is regulated by specific proteins. In the next five years, we will perform scientific studies to better understand how select proteins specifically regulate the biogenesis of the let-7 family of microRNAs. Our studies will provide critical insights into our general understanding of microRNA biogenesis, a fundamental cellular process in the natural sciences that is still not completely understood. In addition, our studies could also help in the development of novel cancer therapeutics.