Phase separation of RNA-binding protein promotes polymerase binding and transcription
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA631979 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11778017_1.fastq.gz | Fastqsanger.gz | |||
| SRR11778017_2.fastq.gz | Fastqsanger.gz | |||
| SRR11778018_1.fastq.gz | Fastqsanger.gz | |||
| SRR11778018_2.fastq.gz | Fastqsanger.gz | |||
| SRR11778019_1.fastq.gz | Fastqsanger.gz |
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Project description:The function of phase separation for many RNA-binding proteins is poorly understood, including FUS (FUSed in sarcoma). FUS binds RNA Pol II and controls phosphorylation of serine-2 (Ser2P). We uncovered a FUS activity involving no interactions with the polymerase. FUS could activate transcription of a non-eukaryote polymerase by preventing RNA invasion of DNA to form R-loops. This activity required binding to the nascent transcript and phase separation. We confirmed the activity in human cells using DRIP-seq, where R-loop sites formed were consistent with characteristic features of FUS activity, including transcription start sites where Ser2P signals accumulate after FUS knockdown. R-loop sites were enriched for sequences favored by the degenerate binding specificity of FUS. FUS also regulated R-loops near active retrotransposons and regions associated with DNA repeat expansion disorders. These findings offer a unified model that incorporates RNA-binding and phase separation to guard against instability from disruptive nucleic acid structures.
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