Long Intervening Noncoding RNAs (lincRNAs): Developmental Functions and Molecular Mechanisms of Action

Objetivo

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.

Ámbito científico

Régimen de financiación

ERC-SG - ERC Starting Grant

Institución de acogida

INSTITUT CURIE

Aportación de la UE

€ 1 499 976,00

Dirección

RUE D ULM 26
75231 Paris
Francia

Región

Ile-de-France Ile-de-France Paris

Tipo de actividad

Research Organisations

Contacto administrativo

Sylvie Le Coidic (Ms.)

Investigador principal

Alena Shkumatava (Dr.)

Enlaces

Contactar con la organización Sitio web

Coste total

Sin datos

Beneficiarios (1)