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Updated: May 9, 2026

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Published on: March 28, 2025
SnoRNA U50 levels are regulated by cell proliferation and rRNA transcription
Annalisa Pacilli1, Claudio Ceccarelli, Davide Treré
1Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant'Orsola-Malpighi University Hospital, Bologna 40138, Italy. annalisa.pacilli@gmail.com
Abstract:
rRNA post transcriptional modifications play a role in cancer development by affecting ribosomal function. In particular, the snoRNA U50, mediating the methylation of C2848 in 28S rRNA, has been suggested as a potential tumor suppressor-like gene playing a role in breast and prostate cancers and B-cell lymphoma. Indeed, we observed the downregulation of U50 in colon cancer cell lines as well as tumors. We then investigated the relationship between U50 and proliferation in lymphocytes stimulated by phytohemagglutinin (PHA) and observed a strong decrease in U50 levels associated with a reduced C2848 methylation. This reduction was due to an alteration of U50 stability and to an increase of its consumption. Indeed, the blockade of ribosome biogenesis induced only an early decrease in U50 followed by a stabilization of U50 levels when ribosome biogenesis was almost completely blocked. Similar results were found with other snoRNAs. Lastly, we observed that U50 modulation affects ribosome efficiency in IRES-mediated translation, demonstrating that changes in the methylation levels of a single specific site on 28S rRNA may alter ribosome function. In conclusion, our results link U50 to the cellular proliferation rate and ribosome biogenesis and these findings may explain why its levels are often greatly reduced in cancers.
Insights
Small nucleolar RNA U50 (U50) downregulation in colon cancer correlates with reduced ribosomal RNA methylation and impaired ribosome function. This suggests U50’s role in regulating cell proliferation and its potential as a tumor suppressor.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Post-transcriptional modifications of ribosomal RNA (rRNA) are crucial for ribosomal function and implicated in cancer development.
- Small nucleolar RNA U50 (U50) targets C2848 methylation in 28S rRNA and has been proposed as a tumor suppressor in various cancers.
Purpose of the Study:
- To investigate the role of U50 in colon cancer and its impact on cellular proliferation and ribosome function.
- To explore the mechanisms underlying U50 downregulation in cancer.
Main Methods:
- Analysis of U50 levels in colon cancer cell lines and tumors.
- Investigating U50 expression and C2848 methylation in phytohemagglutinin-stimulated lymphocytes.
- Assessing U50 stability and consumption under conditions of blocked ribosome biogenesis.
- Evaluating the effect of U50 modulation on IRES-mediated translation.
Main Results:
- U50 was found to be downregulated in colon cancer cell lines and tumors.
- Decreased U50 levels in lymphocytes correlated with reduced C2848 methylation and were linked to altered U50 stability and increased consumption.
- Blockade of ribosome biogenesis led to an initial decrease in U50, followed by stabilization.
- U50 modulation was shown to affect ribosome efficiency in IRES-mediated translation.
Conclusions:
- The study links U50 to cellular proliferation rates and ribosome biogenesis.
- Findings suggest that reduced U50 levels contribute to altered ribosome function and may explain its downregulation in cancers.
- U50's role in regulating ribosome efficiency highlights its potential significance in cancer development.
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