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FUS, RNA and the nucleolus

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posted on 2023-06-09, 04:17 authored by Duncan MooreDuncan Moore
Fused-in-sarcoma (FUS) is an RNA binding protein, thought to be involved in a wide variety of cellular processes, and mutations in FUS are known to be causative for amyotrophic lateral sclerosis (ALS). The mechanism of pathogenesis for ALS has not been established but it has been proposed that dysfunction in cellular functions involving RNA could be responsible. Investigations into a FUS-ALS patient cell line showed sensitivity to the transcriptional inhibitor camptothecin (CPT) and demonstrated constitutively fragmented nucleoli, a phenotype that has been associated with rRNA dysfunction, as well as a possible defect in ribosomal RNA (rRNA) maturation. In addition a reversible relocalisation of FUS to the nucleolus in response to inhibition of RNA polymerase II was observed in all cell lines examined. This relocalisation appeared to be dependent on the activity of phosphodiesterase 8 (PDE8) and on the presence of rRNA, as pre-inhibition of RNAP I (which produces rRNA) prevented relocalisation of FUS. However treatment of both RNAP I and RNAP II at the same time resulted in FUS relocalisation and the protein remaining in the nucleolus for hours if inhibition was maintained - long after RNA would be depleted at the site were RNAP I inhibited in isolation. These findings suggest that FUS may have a role in protecting pre-rRNA transcripts from degradation during transcriptional stress.

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  • Published version

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351.0

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  • Biochemistry Theses

Qualification level

  • doctoral

Qualification name

  • phd

Language

  • eng

Institution

University of Sussex

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  • Yes

Legacy Posted Date

2016-12-19

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