A ribosomal pseudouridine drives an oncogenic translation program
- 1Universite de Sherbrooke
Abstract
Ribosome heterogeneity can regulate translation, but how changes in ribosome chemistry reshape cellular programs and contribute to diseases such as cancer remains incompletely understood. Here we show that SNORA81-guided pseudouridylation at a single 28S ribosomal RNA site, U4636, links ribosome heterogeneity to selective translation and ovarian cancer cell proliferation. This partially modified site contacts eL31 near the peptide-exit region. SNORA81 depletion reduces U4636 pseudouridylation and changes ribosome occupancy in relation to codon identity and nascent-peptide properties without broadly disrupting rRNA processing or bulk polysome profiles. Depletion also redistributes mRNAs with distinct GC content and amino-acid composition across polysomes, with corresponding protein-abundance changes in selected cancer-associated targets. Wild-type SNORA81, but not a guide-region mutant, restores proliferation. Together, these findings support a "sno-balling" model in which altered abundance of a single snoRNA propagates through rRNA modification, selective ribosome engagement and protein output to reshape cancer-associated gene expression and cell behavior.
Related
- A Ribosomal RNA modification regulates translation of PI3K/AKT activators in high-grade serous ovarian carcinoma
- Placental LBX1 dysregulation drives ribosomal dysfunction and unfolded protein response in spontaneous preterm birth
- Non-coding RNA 7SK drives tumor resistance by coupling local oncogenic activation with global transcriptional repression
- Translation and Cultural Adaptation of the Home Graded Repetitive Arm Supplementary Program (Home-GRASP) for Stroke Survivors in Spain.
- The EF1α promoter of cilta-cel drives a highly effective GZMK⁺ transcriptional program.
BibTeX
@misc{fauchergiguere2026ribosomal,
title = {{A ribosomal pseudouridine drives an oncogenic translation program}},
author = {L. Faucher-Giguere and A. Rivera-Pizana and B. Seguineau de Preval and E. Fafard-Couture and G. Deschamps-Francoeur and V. Marchand and Y. Motorin and C. Barchet and B. P. Klaholz and T. Azad and M. S. Scott and S. Abou Elela},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.757013},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.757013v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A ribosomal pseudouridine drives an oncogenic translation program
AU - L. Faucher-Giguere
AU - A. Rivera-Pizana
AU - B. Seguineau de Preval
AU - E. Fafard-Couture
AU - G. Deschamps-Francoeur
AU - V. Marchand
AU - Y. Motorin
AU - C. Barchet
AU - B. P. Klaholz
AU - T. Azad
AU - M. S. Scott
AU - S. Abou Elela
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.757013
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.757013v1
AB - Ribosome heterogeneity can regulate translation, but how changes in ribosome chemistry reshape cellular programs and contribute to diseases such as cancer remains incompletely understood. Here we show that SNORA81-guided pseudouridylation at a single 28S ribosomal RNA site, U4636, links ribosome heterogeneity to selective translation and ovarian cancer cell proliferation. This partially modified site contacts eL31 near the peptide-exit region. SNORA81 depletion reduces U4636 pseudouridylation and changes ribosome occupancy in relation to codon identity and nascent-peptide properties without broadly disrupting rRNA processing or bulk polysome profiles. Depletion also redistributes mRNAs with distinct GC content and amino-acid composition across polysomes, with corresponding protein-abundance changes in selected cancer-associated targets. Wild-type SNORA81, but not a guide-region mutant, restores proliferation. Together, these findings support a "sno-balling" model in which altered abundance of a single snoRNA propagates through rRNA modification, selective ribosome engagement and protein output to reshape cancer-associated gene expression and cell behavior.
ER -