Project description DEENESFRITPL The novel cellular master regulators of RNA processing Messenger RNAs (mRNAs) transit from transcription in the nucleus to translation followed by decomposition in the cytoplasm. Similarly, ribosomal RNAs (rRNAs) migrate through the nucleolus where they gradually interact with ribosomal proteins to assemble functional ribosomes. Many RNA processing steps occur in membraneless organelles formed by liquid-liquid phase separation (e.g. the nucleolus). The EU-funded DDX TRANSIT project aims to provide key novel insight to understand RNA processing. It is based on the project researcher's discovery that the family of DEAD-box ATPases (DDXs) are indeed the master regulators of RNA-containing membraneless organelles. The project proposes that cells use DDX-controlled condensate formations to establish an RNA transit map for the cellular traffic of mRNA and rRNA molecules to control RNA processing. Show the project objective Hide the project objective Objective Life ultimately depends on the tight control of gene expression, which requires an ordered and efficient processing of various RNA molecules. Messenger RNAs (mRNAs) – bound by a constantly changing coat of passenger proteins - transit from transcription in the nucleus to translation and ultimately decay in the cytoplasm. Similarly, ribosomal rRNAs migrate through the nucleolus where they gradually en-counter ribosomal proteins to assemble functional ribosomes. Still, we know very little about the pro-cesses that orchestrate this flux of RNA in a temporal and spatial manner.Intriguingly, many RNA processing steps occur in membraneless organelles formed by liquid-liquid phase separation, e.g. nuclear speckles or the nucleolus, but the function of condensate formation in RNA processing is not known. I have discovered that the family of DEAD-box ATPases (DDXs) are master regulators of RNA-containing membraneless organelles, from bacteria to man. DDXs use their low-complexity domains and ATPase activity to regulate condensate dynamics and RNA flux through these compartments.I propose that cells use DDX-controlled condensate ‘stations’ to establish an RNA ‘transit map’ to reg-ulate the cellular flux of mRNA and rRNA molecules and to spatially and temporally control RNA pro-cessing. In three work packages, I will (1) characterize central DDXs that control mRNA flux and use DDX mutants as unique tools to map passenger protein changes along the life of an mRNA; (2) charac-terize how DDXs regulate the formation of the phase-separated nucleolar environment and facilitate the flux of rRNA during ribosome assembly; (3) dissect how DDX condensates function as biomolecular filters to selectively enrich or exclude proteins, and how selectivity contributes to the remodeling of the RNA protein coat and directional RNA flux.Our research will provide key novel insight into our understanding of RNA processing and uncover novel layers of gene expression regulation. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsRNA Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-STG - ERC STARTING GRANTS Call for proposal ERC-2020-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution UNIVERSITAT BASEL Net EU contribution € 1 499 845,00 Address PETERSPLATZ 1 4051 Basel Switzerland See on map Region Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 845,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAT BASEL Switzerland Net EU contribution € 1 499 845,00 Address PETERSPLATZ 1 4051 Basel See on map Region Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 845,00
