The roles of microRNAs and transcription factors in gene regulation and tissue specific expression

MicroRNAs (miRNAs) were identified as a large group of regulatory genes in 2001, and increasing research has revealed these genes to be important in development, including differentiation, proliferation, and apoptosis. Many miRNAs seem to have tissue-spec ific expression patterns, which suggest that together with transcription factors, miRNAs may be crucial for establishing and maintaining tissue specific gene regulation. These mechanisms are currently poorly understood, however. Most miRNAs likely have m any target genes, but current methods have had limited success in predicting these targets - possibly because many miRNA targets are coordinately regulated by multiple miRNAs, whereas most current methods only consider one miRNA at the time. We have recen tly determined some of the critical factors for cooperative miRNA regulation and are extending our current miRNA target prediction tool to take these factors into account. Here we will use our improved understanding of miRNA regulation to study how miRNA s and transcription factors coordinately regulate genes. We will focus on two specific problems: cell-cycle regulation and aberrant miRNA expression during virus infections. By combining computational and lab analysis, we will develop computational models that can increase our understanding of gene regulatory networks. Furthermore, we will use cell-type specific miRNA expression patterns to develop tools for in vivo cell-type specific gene knockdown and transgene expression. Our collaborators will use the se tools to study the function of specific neurons in rat brains, but the technology can also be used for general cell-type specific expression studies.