Ribosome quality control activity potentiates vaccinia virus protein synthesis during infection
العنوان: | Ribosome quality control activity potentiates vaccinia virus protein synthesis during infection |
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المؤلفون: | Marilyn Leonard, Eric J. Bennett, Amit Fulzele, Elayanambi Sundaramoorthy, Andrew P. Ryan, Matthew D. Daugherty |
المصدر: | Journal of Cell Science article-version (VoR) Version of Record |
بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | Quality Control, Ubiquitylation, Viral protein, viruses, Vaccinia virus, Biology, medicine.disease_cause, Ribosome, Virus, Integrated stress response, chemistry.chemical_compound, Ubiquitin, Transcription (biology), Vaccinia, medicine, Humans, Eukaryotic Small Ribosomal Subunit, ZNF598, Translation (biology), Cell Biology, Cell Biology and Disease, Cell biology, HEK293 Cells, Proteostasis, chemistry, Viral replication, Protein Biosynthesis, biology.protein, Carrier Proteins, Ribosomes, Research Article |
الوصف: | Viral infection both activates stress signaling pathways and redistributes ribosomes away from host mRNAs to translate viral mRNAs. The intricacies of this ribosome shuffle from host to viral mRNAs are poorly understood. Here, we uncover a role for the ribosome-associated quality control (RQC) factor ZNF598 during vaccinia virus mRNA translation. ZNF598 acts on collided ribosomes to ubiquitylate 40S subunit proteins uS10 (RPS20) and eS10 (RPS10), initiating RQC-dependent nascent chain degradation and ribosome recycling. We show that vaccinia infection enhances uS10 ubiquitylation, indicating an increased burden on RQC pathways during viral propagation. Consistent with an increased RQC demand, we demonstrate that vaccinia virus replication is impaired in cells that either lack ZNF598 or express a ubiquitylation-deficient version of uS10. Using SILAC-based proteomics and concurrent RNA-seq analysis, we determine that translation, but not transcription of vaccinia virus mRNAs is compromised in cells with deficient RQC activity. Additionally, vaccinia virus infection reduces cellular RQC activity, suggesting that co-option of ZNF598 by vaccinia virus plays a critical role in translational reprogramming that is needed for optimal viral propagation. Summary: The ribosome-associated quality control factor ZNF598, which senses ribosome collisions, is a host factor necessary for vaccinia viral protein synthesis. |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::752eb702d31302c8c5510f34c2c67faf https://doi.org/10.1101/2020.11.12.380634 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....752eb702d31302c8c5510f34c2c67faf |
قاعدة البيانات: | OpenAIRE |
الوصف غير متاح. |