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Nucleolar disruption leads to the spatial separation of key 18S rRNA processing factors

Lookup NU author(s): Dr Amy Erhorn, Andy Knox, Dr Nick Watkins

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Abstract

Many chemotherapeutic drugs cause the downregulation of ribosome production and the disruption of nucleolar function. This stabilizes p53 and leads to either cell cycle arrest or apoptosis. It is not clear, however, how these agents cause nucleolar disruption and block ribosome production. The small subunit (SSU) processome, which has been primarily studied in yeast, is responsible for the processing of the 18S rRNA and assembly of the small ribosomal subunit. Here we have characterized the human homologs of seven SSU processome components. Furthermore, we have investigated the effects of three chemotherapeutic drugs, Actinomycin D (ActD), camptothecin (CPT) and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) on the subcellular distribution of key SSU processome components and the formation of this processing complex. Interestingly, ActD- and DRB-treatment resulted in the majority of U3 small nucleolar RNP (snoRNP) localizing separately to other key components of the SSU processome. All three agents affected RNA polymerase I transcription, primarily at the level of elongation but only ActD resulted in a clear reduction in SSU processome levels. Taken together, our data indicate that different chemotherapeutic agents, each of which initiates a stress response and cause nucleolar disruption, have different effects on the formation and localization of the SSU processome.


Publication metadata

Author(s): Turner AJ, Knox AA, Watkins NJ

Publication type: Article

Publication status: Published

Journal: RNA Biology

Year: 2012

Volume: 9

Issue: 2

Pages: 175-186

Print publication date: 01/02/2012

ISSN (print): 1547-6286

ISSN (electronic): 1555-8584

Publisher: Landes Bioscience

URL: http://dx.doi.org/10.4161/rna.18811

DOI: 10.4161/rna.18811


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