Project description DEENESFRITPL Complete characterisation of undefined long intervening noncoding RNAs In 2003, the Human Genome Project, an extensive multinational collaboration and one of the most ambitious scientific endeavours ever undertaken, produced a genome sequence accounting for over 90 % of the human genome. Following decades of subsequent research, we now know that the very large part of our DNA made up of non-protein-coding regions, so-called intergenic regions, are not superfluous but play key roles in gene regulation. The European Research Council-funded lincSAFARI project will investigate the role(s) of long intervening noncoding RNAs (lincRNAs) in gene regulation during cell differentiation. The team will employ comparative genomics, quantitative molecular phenotyping and high-throughput screening along with computational biology to exhaustively describe previously uncharacterised lincRNAs. Show the project objective Hide the project objective Objective It is now clear that many intergenic regions in eukaryotic genomes give rise to a range of processed and regulated transcripts that do not appear to code for functional proteins. A subset of these are long (>200 nt), capped and polyadenylated RNAs transcribed by RNA polymerase II and collectively called long intervening noncoding RNAs or lincRNAs. The recent estimates are that the human genome encodes >10,000 distinct lincRNAs, many of which show tissue-specific expression and are frequently dysregulated in human disease, including neurodegeneration. Given the growing number of lincRNAs implicated in human disease or required for proper development, fundamental questions that need to be addressed are: Which lincRNAs are functional? How is functional information encoded in the lincRNA sequence? Is this information interpreted in the context of the mature or the nascent RNA? What are the identities and functional roles of specific sequence domains within lincRNA genes?Our main hypothesis is that many lincRNA loci play key roles in gene regulation during cell differentiation, both via functionally important transcription events and post-transcriptionally, through the combined action of multiple short sequence domains. We will test this hypothesis using three complementary approaches – comparative genomics, detailed perturbations in mammalian cells followed by quantitative molecular phenotyping, and high-throughput screens for sequences able to carry out specific functions.We propose an interdisciplinary approach combining computational, molecular and stem cell biology. Our methodology will be scalable, allowing us to tackle completely uncharacterized long RNAs and eventually zoom in and study their individual bases. Upon successful accomplishment of the program, we will delineate modes of action of numerous lincRNAs, report sequence patches that are functionally important and understand how specific bases and structures act in concert to drive lincRNA function. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesgeneticsRNAnatural sciencescomputer and information sciencesartificial intelligencecomputational intelligencenatural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2014 - ERC Starting Grant Call for proposal ERC-2014-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator WEIZMANN INSTITUTE OF SCIENCE Net EU contribution € 1 500 000,00 Address Herzl street 234 7610001 Rehovot Israel See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel Net EU contribution € 1 500 000,00 Address Herzl street 234 7610001 Rehovot See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
