The E3 ubiquitin ligase UBR 5 interacts with the H/ ACA ribonucleoprotein complex and regulates ribosomal RNA biogenesis in embryonic stem cells

UBR 5 is an E3 ubiquitin ligase involved in distinct processes such as transcriptional regulation and development. UBR 5 is highly upregulated in embryonic stem cells ( ESC s), whereas its expression decreases with differentiation, suggesting a role for UBR 5 in ESC function. However, little is known about how UBR 5 regulates ESC identity. Here, we define the protein interactome of UBR 5 in ESC s 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 UBR 5 induces an abnormal accumulation of rRNA processing intermediates, resulting in diminished ribosomal levels. Consequently, lack of UBR 5 triggers an increase in p53 levels and a concomitant decrease in cellular proliferation rates. Thus, our results indicate a link between UBR 5 and rRNA maturation.