Related Experiment Video
Updated: May 24, 2026

Analysis of Spliceosomal snRNA Localization in Human Hela Cells Using Microinjection
Published on: August 6, 2019
Nucleolar disruption leads to the spatial separation of key 18S rRNA processing factors
Amy Jane Turner1, Andrew Alexander Knox, Nicholas James Watkins
1Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
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-β-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.
Insights
Chemotherapy drugs disrupt nucleoli and block ribosome production by affecting the small subunit (SSU) processome. Different drugs impact SSU processome formation and localization uniquely, impacting cell cycle arrest and apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Chemotherapeutic agents often induce nucleolar disruption and inhibit ribosome production, leading to p53 stabilization, cell cycle arrest, or apoptosis.
- The precise mechanisms by which these drugs disrupt nucleoli and block ribosome biogenesis remain unclear.
- The small subunit (SSU) processome, crucial for 18S rRNA processing and small ribosomal subunit assembly, is a key player in ribosome production.
Purpose of the Study:
- To characterize human homologs of SSU processome components.
- To investigate the impact of chemotherapeutic drugs (Actinomycin D, camptothecin, DRB) on SSU processome function and localization.
- To elucidate the differential effects of these drugs on nucleolar integrity and ribosome biogenesis.
Main Methods:
- Characterization of human SSU processome component homologs.
- Treatment of cells with Actinomycin D, camptothecin, and DRB.
- Analysis of subcellular localization of SSU processome components using microscopy.
- Assessment of RNA polymerase I transcription and processome formation.
Main Results:
- Actinomycin D and DRB treatments caused mislocalization of U3 small nucleolar RNP (snoRNP) away from other SSU processome components.
- All three drugs affected RNA polymerase I transcription, primarily impacting elongation.
- Only Actinomycin D treatment led to a significant reduction in overall SSU processome levels.
Conclusions:
- Different chemotherapeutic drugs exhibit distinct mechanisms in disrupting nucleolar function and ribosome production.
- The observed effects on SSU processome localization and formation provide insights into drug-induced cellular stress responses.
- Understanding these differential effects is crucial for comprehending chemotherapy-induced cell death pathways.
Related Concept Videos
The Nucleolus
Ribosomal RNA Synthesis
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Chromatin Structure Regulates pre-mRNA Processing
The chromatin structure, especially...
Nuclear Export of mRNA
Nuclear Export of mRNA
Regulation of Nuclear Protein Sorting

