Objective Genome-wide studies have revealed that the majority of vertebrate genomes are transcribed and generate large numbers of long intervening noncoding RNAs (lincRNAs). While there is growing evidence that these molecules have functional importance for diverse cellular processes, such as dosage compensation, transcriptional regulation, and reprogramming, the role of lincRNAs in normal development remains elusive. To better understand the function and evolution of lincRNAs, we previously identified over 550 lincRNAs expressed during zebrafish embryonic development. We demonstrated that at least two of these novel lincRNAs, megamind and cyrano, are required for proper embryonic development, in particular for brain morphogenesis and neurogenesis. Remarkably, lincRNA functionality is retained in mammalian orthologs despite rapid evolution and little sequence conservation between human and zebrafish lincRNAs (Ulitsky*, Shkumatava* et al., Cell, 2011).This proposal aims to identify conserved developmental functions of novel lincRNAs and to determine the molecular mechanisms that drive these lincRNA functions (Aims 1 and 2). For mechanistic studies, the initial focus will be on cyrano and megamind. Preliminary evidence suggests that one of these novel molecular mechanisms is through a non-canonical interaction between cyrano and the miRNA pathway (Aim 3). Furthermore, we will investigate the relationship between conserved genomic positions of lincRNAs across vertebrate genomes and their conserved biological functions (Aim 4). The specific aims outlined in this proposal will identify novel regulatory RNAs with important and potentially conserved roles in vertebrate embryonic development, and provide mechanistic insights into how specific lincRNA contribute to normal development. Moreover, we anticipate that this project will contribute to a new synthesis of knowledge of genome function and regulation. Fields of science natural sciencesbiological sciencesdevelopmental biologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution INSTITUT CURIE EU contribution € 1 499 976,00 Address RUE D ULM 26 75231 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Sylvie Le Coidic (Ms.) Principal investigator Alena Shkumatava (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT CURIE France EU contribution € 1 499 976,00 Address RUE D ULM 26 75231 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Sylvie Le Coidic (Ms.) Principal investigator Alena Shkumatava (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
