UNIverse - Public Research Portal
Project cover

DDX TRANSIT

Research Project
 | 
01.02.2021
 - 31.01.2026

DEAD-box ATPases as master regulators of phase-separated compartments to control cellular RNA flux and the remodeling of RNA-protein complexes Life ultimately depends on the tight control of gene expression, which requires an ordered and efficient pro- cessing 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 cyto- plasm. Similarly, ribosomal rRNAs migrate through the nucleolus where they gradually encounter ribosomal proteins to assemble functional ribosomes. Still, we know very little about the processes 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 pro- cessing is not known. I have discovered that the family of DEAD-box ATPases (DDXs) are master regula- tors 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 processing. 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) characterize 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 selec- tively 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.

Funding

DDX TRANSIT

Horizon 2020 ERC (GrantsTool), 02.2021-01.2026 (60)
PI : Hondele, Maria.

Members (1)

Profile Photo

Maria Hondele

Principal Investigator