Objetivo A significant fraction of mammalian genomes is composed of repetitive elements, such as pericentric major satellite repeats. Repetitive elements present a critical challenge to genome stability because these regions are prone to recombination. To safeguard genome integrity, these repetitive sequences are maintained in an epigenetically silent heterochromatic state to prevent mutagenic recombination. A confounding enigma revealed by recent transcriptome-wide studies is that repetitive elements are actively transcribed into noncoding RNAs (ncRNAs). Furthermore, these repeat-derived transcripts are themselves important to maintain the heterochromatic structure at repetitive elements. Nevertheless, it appears that a certain balance must be achieved since overexpression of repeat-derived ncRNAs is a hallmark of the most common types of cancer. How repeat-derived ncRNAs function in epigenetic regulation of heterochromatin is poorly understood. In this proposed study, ncRNAs transcribed from mouse pericentric major satellite repeats will be investigated as a paradigm to understand the precise mechanism of how these ncRNAs regulate heterochromatin formation. The key element of the proposed study is characterizing the function of major satellite RNAs from a structural perspective. This is a novel and promising approach because the functions of RNA molecules are intimately linked with their ability to fold into complex structures. A possible scenario is that accurate folding of major satellite RNA directs the local recruitment of chromatin complexes to pericentric loci. To address this hypothesis, the proposed research programme aims to achieve the following: (i) determine the structure of major satellite RNAs; (ii) determine if major satellite RNAs are divided into functional domains and how this relates to the structure; and (iii) determine how the structure of major satellite RNAs influence their interaction with pericentric DNA and chromatin-associated proteins. Ámbito científico engineering and technologymechanical engineeringvehicle engineeringaerospace engineeringsatellite technologynatural scienceschemical sciencesorganic chemistryheterocyclic compoundsnatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Palabras clave noncoding RNA RNA structure RNA-protein complexes heterochromatin pericentric heterochromatin repetitive elements Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Convocatoria de propuestas H2020-MSCA-IF-2014 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinador MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Aportación neta de la UEn € 159 460,80 Dirección HOFGARTENSTRASSE 8 80539 Munchen Alemania Ver en el mapa Región Bayern Oberbayern München, Kreisfreie Stadt Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 159 460,80