Descripción del proyecto
¿Cómo se regulan los ARN reguladores?
El ARN (o RNA, por sus siglas en inglés) no codificante (ARNnc) corresponde a una clase de moléculas de ARN que, si bien no codifican proteínas, intervienen directamente en diversos procesos celulares, incluida la regulación génica. Cada vez disponemos de más pruebas acerca del papel de los ARNnc en los mecanismos de defensa del hospedador contra los virus, ya sea uniéndose al ARN viral o regulando las respuestas inmunitarias y la inflamación del hospedador. A partir de estas premisas, el equipo del proyecto RegulRNA, financiado por el Consejo Europeo de Investigación, se centrará en el estudio de los microARN, conocidos por su capacidad para regular la expresión génica uniéndose al ARN mensajero y facilitando su degradación. El objetivo central del proyecto pasa por investigar cómo se regulan los procesos de silenciamiento del ARN durante las infecciones víricas adoptando para ello un enfoque multidisciplinar.
Objetivo
Small and large non-coding RNAs are essential components at the heart of gene expression regulation. The past fifteen years have witnessed the emergence of a new field of research impacting diverse domains of biology. Among these, virology is no exception and discoveries such as the antiviral role of RNA silencing, virus-encoded microRNAs (miRNAs), or miRNA-based regulation of viruses have notably shifted our views of host-virus interactions. Although we know a lot about the mechanisms of action of ncRNAs, and their role in the context of viral infections, we know much less regarding the control of the regulatory RNAs themselves. In other words, how are the regulators regulated? To provide answers to this burning question, we propose to use different viruses as models to investigate the various levels where modulation of regulatory RNA can occur. Thus, we will study the importance of RNA secondary and tertiary structure as well as accessory proteins in the regulation of miRNA primary transcript processing. In a second axis, we propose to investigate how the functional, mature miRNAs can be controlled. To this end, we will focus on the mechanisms of target-mediated miRNA decay and the role of competing endogenous RNAs. We will finally turn to the regulation of antiviral RNA silencing. Although it seems that this kind of defence mechanism exist in mammalian cells, it is not yet clear how physiologically relevant it is and how it interfaces with other innate immune mechanisms. In this multidisciplinary project, we will use a combination of techniques ranging from bioinformatics to cellular biology to achieve our goal to get a comprehensive view of how RNA silencing processes are regulated during virus infection.
Ámbito científico
- medical and health scienceshealth sciencesinfectious diseasesRNA viruses
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesgeneticsRNA
- medical and health scienceshealth sciencesinfectious diseasesDNA viruses
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
75794 Paris
Francia