FUS facilitates gene body export from nuclear condensates
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA975594 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24716300.fastq.gz | Fastqsanger.gz | |||
| SRR24716301.fastq.gz | Fastqsanger.gz | |||
| SRR24716284.fastq.gz | Fastqsanger.gz | |||
| SRR24716285.fastq.gz | Fastqsanger.gz | |||
| SRR24716286.fastq.gz | Fastqsanger.gz |
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Project description:Biomolecular condensates formed by phase separation offer a confined space where protein-protein interactions (PPIs) facilitate distinct biochemical reactions. As their aberrant behavior is associated with disease, it is crucial to understand the molecular organization of PPIs within condensates. Using quantitative time-resolved crosslinking mass spectrometry (XL-MS) we directly and specifically monitor PPIs and protein dynamics inside condensates formed by the protein fused in sarcoma (FUS) and identify its folded RNA recognition motif (RRM) as a key player of aberrant molecular aging. We find that the chaperone HspB8, but not a disease-associated mutant, prevents FUS aging. In XL-MS and partitioning experiments we find that the disordered region of HspB8 directs its α-crystallin domain (αCD) into FUS droplets where HspB8 prevents aging via condensate-specific αCD–RRM interactions. We propose that chaperones like HspB8 prevent aberrant phase transitions by stabilizing aggregation prone folded domains inside condensates in times of cellular stress.
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Project description:Biomolecular condensates formed by phase separation offer a confined space where protein-protein interactions (PPIs) facilitate distinct biochemical reactions. As their aberrant behavior is increasingly associated with disease, it is crucial to understand the molecular organization of PPIs within condensates. Using quantitative and time-resolved crosslinkingmass spectrometry we directly and specifically monitor PPIs and protein dynamics of fused in sarcoma (FUS) condensates and identify its RNA recognition motif (RRM) as a key player of condensate-specific PPIs and aging. We find that the chaperone HspB8, but not a disease-associated mutant, prevents FUS aging. The disordered region of HspB8 directs its α-crystallin domain (αCD) into FUS condensates. Here, RRM unfolding drives aggregation but binding of HspB8 via a droplet-specific αCD – RRM interface significantly delays the onset of aging. We propose that chaperones such as HspB8 prevent aberrant phase transitions by stabilizing aggregation prone RNA binding domains in times of cellular stress.
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