The E3 ubiquitin ligase UBR5 interacts with the H/ACA ribonucleoprotein complex and regulates ribosomal RNA biogenesis in embryonic stem cells
| Autor: | Niels H. Gehring, Isabel Saez, Moritz Horn, Hyun Ju Lee, David Vilchez, Seda Koyuncu, Virginia Kroef, Christoph Dieterich, Martin S. Denzel, Jennifer V. Gerbracht |
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| Rok vydání: | 2019 |
| Předmět: |
Ubiquitin-Protein Ligases
Biophysics Biochemistry Ribosome 03 medical and health sciences Mice Downregulation and upregulation Structural Biology Genetics Transcriptional regulation Animals Humans RNA Processing Post-Transcriptional RRNA processing Molecular Biology Cells Cultured Embryonic Stem Cells 030304 developmental biology 0303 health sciences biology Chemistry 030302 biochemistry & molecular biology Cell Biology Ribosomal RNA Embryonic stem cell Ubiquitin ligase Cell biology HEK293 Cells Ribonucleoproteins RNA Ribosomal biology.protein Tumor Suppressor Protein p53 Biogenesis |
| Zdroj: | FEBS Lett |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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