The E3 ubiquitin ligase UBR5 interacts with the H/ACA ribonucleoprotein complex and regulates ribosomal RNA biogenesis in embryonic stem cells

FEBS Letters
Isabel SaezDavid Vilchez

Abstract

UBR5 is an E3 ubiquitin ligase involved in distinct processes such as transcriptional regulation and development. UBR5 is highly upregulated in embryonic stem cells (ESCs), whereas its expression decreases with differentiation, suggesting a role for UBR5 in ESC function. However, little is known about how UBR5 regulates ESC identity. Here, we define the protein interactome of UBR5 in ESCs and find interactions with distinct components of the H/ACA ribonucleoprotein complex, which is required for proper maturation of ribosomal RNA (rRNA). Notably, loss of UBR5 induces an abnormal accumulation of rRNA processing intermediates, resulting in diminished ribosomal levels. Consequently, lack of UBR5 triggers an increase in p53 levels and a concomitant decrease in cellular proliferation rates. Thus, our results indicate a link between UBR5 and rRNA maturation.

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Citations

Jan 23, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Maud de Dieuleveult, Benoit Miotto
Feb 27, 2020·Cells·Mathieu GabutSébastien Durand
Feb 13, 2021·Journal of Gastroenterology and Hepatology·Yue WuJianping Gong
Sep 6, 2020·Current Opinion in Cell Biology·Ernesto LlamasDavid Vilchez
Jul 18, 2021·Nature Reviews. Molecular Cell Biology·James A SabaFiona M Watt

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