Over 90% of transcriptional output from the human genome is estimated to be noncoding. Noncoding RNAs (ncRNA) have been implicated in a myriad of biological processes including chromatin remodeling, development, differentiation, and stress responses. Yet in spite of genome annotations which place the number of ncRNA loci in the thousands, little is known about the projected 3000-4000 ncRNA genes present in the human genome. The proposed research seeks to shed light on this largely neglected component of the transcriptome. Using a functional genomics strategy, putative ncRNAs conserved between human and mouse will be identified and then targeted via RNA-interference with a custom built siRNA library. Screens of this library with a variety of cell-based screens representing fundamental cellular processes and signaling pathways will link the mouse-human conserved ncRNAs to biological function. Follow-up characterization will define the role of these functional ncRNAs. Additionally, a subset of ncRNAs were recognized to reside immediately upstream of protein-coding genes where they may have a role in the cis regulation of these genes. Further examination will define their regulatory relationship and biological significance.
