A Ribosomal RNA modification regulates translation of PI3K/AKT activators in high-grade serous ovarian carcinoma
- 1Universite de Sherbrooke
Abstract
PI3K/AKT signalling is a key driver of ovarian cancer progression and an important therapeutic target. Its deregulation is usually explained by genetic changes and altered signalling at the cell surface. Here, we identify an additional layer of pathway control, in which a change in the level of a cancer-associated ribosomal RNA modification alters the translation of proteins that regulate PI3K/AKT activity. SNORA81 is a high-grade serous ovarian carcinoma-associated H/ACA small nucleolar RNA that directs pseudouridylation of 28S ribosomal RNA at position U4636. Integration of tumour transcriptomes with independent SNORA81-depletion datasets identified 22 SNORA81-linked transcripts with reversed disease-associated expression, 19 of them linked to PI3K/AKT signalling. SNORA81 depletion reduced AKT phosphorylation, impaired cell growth, migration, and altered cell-cycle distribution. Molecularly, polysome profiling following SNORA81 depletion identified 524 mRNAs with altered ribosome association, 485 of which changed independently of RNA abundance and included 29 PI3K/AKT regulators. SNORA81 depletion reduced ribosome association of ITGB4, RASGRP2, IGF1 and FGF18 transcripts, and reduced ITGB4 and RASGRP2 protein abundance. IRAK1 and SPC24 acted as downstream RNA-response genes contributing to selected SNORA81-associated phenotypes. ITGB4 expression partially restored cell growth and restored downstream RNA responses after SNORA81 depletion. These findings identify rRNA modification as a translational regulator of PI3K/AKT signalling in ovarian cancer.
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BibTeX
@misc{pizana2026ribosomal,
title = {{A Ribosomal RNA modification regulates translation of PI3K/AKT activators in high-grade serous ovarian carcinoma}},
author = {A. Rivera Pizana and L. Faucher-Giguere and M. S. Scott and S. Abou Elela},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.757003},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.757003v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A Ribosomal RNA modification regulates translation of PI3K/AKT activators in high-grade serous ovarian carcinoma
AU - A. Rivera Pizana
AU - L. Faucher-Giguere
AU - M. S. Scott
AU - S. Abou Elela
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.757003
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.757003v1
AB - PI3K/AKT signalling is a key driver of ovarian cancer progression and an important therapeutic target. Its deregulation is usually explained by genetic changes and altered signalling at the cell surface. Here, we identify an additional layer of pathway control, in which a change in the level of a cancer-associated ribosomal RNA modification alters the translation of proteins that regulate PI3K/AKT activity. SNORA81 is a high-grade serous ovarian carcinoma-associated H/ACA small nucleolar RNA that directs pseudouridylation of 28S ribosomal RNA at position U4636. Integration of tumour transcriptomes with independent SNORA81-depletion datasets identified 22 SNORA81-linked transcripts with reversed disease-associated expression, 19 of them linked to PI3K/AKT signalling. SNORA81 depletion reduced AKT phosphorylation, impaired cell growth, migration, and altered cell-cycle distribution. Molecularly, polysome profiling following SNORA81 depletion identified 524 mRNAs with altered ribosome association, 485 of which changed independently of RNA abundance and included 29 PI3K/AKT regulators. SNORA81 depletion reduced ribosome association of ITGB4, RASGRP2, IGF1 and FGF18 transcripts, and reduced ITGB4 and RASGRP2 protein abundance. IRAK1 and SPC24 acted as downstream RNA-response genes contributing to selected SNORA81-associated phenotypes. ITGB4 expression partially restored cell growth and restored downstream RNA responses after SNORA81 depletion. These findings identify rRNA modification as a translational regulator of PI3K/AKT signalling in ovarian cancer.
ER -