Structure and function of repeat-derived non-coding RNAs in epigenetic regulation of mammalian pericentric heterochromatin

Información del proyecto

RNA-SHAPE

Identificador del acuerdo de subvención: 657988

DOI

10.3030/657988

Proyecto finalizado el 9 Agosto 2016

Fecha de la firma de la CE 12 Marzo 2015

Fecha de inicio 1 Mayo 2015

Fecha de finalización 30 Abril 2017

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 159 460,80

Aportación de la UE

€ 159 460,80

Coordinado por

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

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 (EuroSciVoc)

• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › ácido nucleico
• ciencias naturales › ciencias químicas › química orgánica › compuestos heterocíclicos
• ciencias naturales › ciencias biológicas › genética › ARN
• ciencias naturales › ciencias biológicas › genética › genoma
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas › enzima

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 PROGRAMA PRINCIPAL
  
• 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)
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2014

Coordinador

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

• Aportación neta de la UEn: € 159 460,80
• Dirección: HOFGARTENSTRASSE 8 ; 80539 MUNCHEN ; Alemania
• Región: Bayern › Oberbayern › München, Kreisfreie Stadt
• Tipo de actividad: Research Organisations
• Coste total: € 159 460,80