Title: Cis-acting gene regulationby long noncoding RNAs.
It is now clear that many intergenic regions in eukaryoticgenomes give rise to a range of processed and regulated transcripts that do notappear to code for functional proteins. A subset of these are long (>200nt), capped, and polyadenylated RNAs transcribed by RNA polymerase II andcollectively called long noncoding RNAs (lncRNAs). The recent estimates arethat the human genome may have >50,000 distinct lncRNA-producing loci, manyof which show tissue-specific activity and dysregulation in human disease,including cancer and neurodegeneration.
Giventhe growing number of lncRNAs implicated in human disease or required forproper development, fundamental questions that need to be addressed are: WhichlncRNAs are functional? How is functional information encoded in the lncRNAsequence? Is this information interpreted in the context of the mature or thenascent RNA? What are the identities and functional roles of specific sequencedomains within lncRNA genes? These are challenging questions, primarilybecause of the substantial heterogeneity in mechanisms utilized by lncRNAs andthe current paucity of lncRNAs with well-understood mechanisms. We are tacklingthese questions by combination of experimental methods with a focus on lncRNAfunctions in early cell fate decisions and computational methods focused onlncRNA evolution. I will describe our efforts to decode conserved combinationsof short functional sequence elements in lncRNAs, with a particular focus onthe Chaserr/Chd2 and Silc1/Sox11 pathways.
Host: Sagi Levy