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Formation and function of membraneless organelles

Cells not only use membranes but also self-assembly processes to organize their content. We study the formation, regulation and function of membraneless organelles, in particular those associated with RNA processing.

Life ultimately depends on the tight control of gene expression, which requires ordered and efficient processing of various RNA molecules. Yet, we know very little about the cellular processes that orchestrate the flux of RNA in a temporal and spatial manner, and thus ultimately the fate of an RNA. 

Phase separation and membraneless organelles
Liquid-liquid phase separation is a self-assembly process that concentrates specific proteins and nucleic acids into highly dynamic condensates, similar to the formation of oil droplets in water. Many of these non-membrane bound organelles contain RNA, or are associated with RNA processing, for example nuclear speckles, the nucleolus, stress granules or P-bodies. Although they have been described for a long time, we still know little about the formation and function of these and other membraneless organelles, and how condensation influences certain biochemical processes such as RNA processing. 

Family of enzymes are master regulators of condensates
We have discovered that the protein family of DEAD-box ATPases has an essential function in regulating the assembly and disassembly of various RNA-containing membraneless organelles, from bacteria to man. These enzymes regulate the formation and dynamics of condensates, and the accumulation of RNA in these compartments. We use biochemical reconstitutions, biophysical measurements, screening approaches and imaging to dissect which human DEAD-box ATPases regulate which membraneless organelles, and to characterize their biochemical function. 

How do condensates influence the cellular flux and processing of RNA?
Messenger RNAs transit from the nucleus, the site of transcription, to the cytoplasm, where they are translated into proteins and ultimately decay. Many RNA processing steps occur in, or are associated with membraneless organelles. We want to investigate how these condensates influence the cellular ‘flux’ of RNAs, and whether they impact how efficiently an RNA is translated or decayed.

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