|
| Status |
Public on Apr 14, 2021 |
| Title |
Ribosome quality control activity potentiates vaccinia virus protein synthesis during infection |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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 and eS10 initiating RQC-dependent nascent chain degradation and ribosome recycling
We show that vaccinia infection in human cells 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 which either lack ZNF598 or express a ubiquitylation deficient version of uS10
Using SILAC-based proteomics and concurrent RNAseq analysis, we determine that translation and 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.
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| |
|
| Overall design |
6 samples were analyzed in triplicates
|
| |
|
| Contributor(s) |
Sundaramoorthy E, Bennett E |
| Citation(s) |
33912921 |
| |
| Submission date |
Jan 28, 2021 |
| Last update date |
May 20, 2021 |
| Contact name |
Elayanambi Sundaramoorthy |
| Organization name |
University of California San Diego
|
| Department |
Section of cell and developmental biology
|
| Lab |
Bennett lab
|
| Street address |
9500, GILMAN DRIVE, la jolla
|
| City |
san diego |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (18)
|
| GSM5048999 |
HCT116-uS10-KI (RPS20-KI)-mock-replicate 1 [RPS20_KI_1] |
| GSM5049000 |
HCT116-uS10-KI (RPS20-KI)-mock-replicate 2 [RPS20_KI_2] |
| GSM5049001 |
HCT116-uS10-KI (RPS20-KI)-mock-replicate 3 [RPS20_KI_3] |
| GSM5049002 |
HCT-116- 4hpi-VACV-WR -replicate 1 [PAR_BC_4hpi_1] |
| GSM5049003 |
HCT-116- 4hpi-VACV-WR -replicate 2 [PAR_BC_4hpi_2] |
| GSM5049004 |
HCT-116- 4hpi-VACV-WR -replicate 3 [PAR_BC_4hpi_3] |
| GSM5049005 |
HCT116-uS10-KI (RPS20-KI)-4hpi-VACV-WR-replicate 1 [RPS20_KI_4hpi_1] |
| GSM5049006 |
HCT116-uS10-KI (RPS20-KI)-4hpi-VACV-WR-replicate 2 [RPS20_KI_4hpi_2] |
| GSM5049007 |
HCT116-uS10-KI (RPS20-KI)-4hpi-VACV-WR-replicate 3 [RPS20_KI_4hpi_3] |
| GSM5049008 |
HCT-116- 8hpi-VACV-WR -replicate 1 [PAR_BC_8hpi_1] |
| GSM5049009 |
HCT-116- 8hpi-VACV-WR -replicate 2 [PAR_BC_8hpi_2] |
| GSM5049010 |
HCT-116- 8hpi-VACV-WR -replicate 3 [PAR_BC_8hpi_3] |
| GSM5049011 |
HCT116-uS10-KI (RPS20-KI)-8hpi-VACV-WR-replicate 1 [RPS20_KI_8hpi_1] |
| GSM5049012 |
HCT116-uS10-KI (RPS20-KI)-8hpi-VACV-WR-replicate 2 [RPS20_KI_8hpi_2] |
| GSM5049013 |
HCT116-uS10-KI (RPS20-KI)-8hpi-VACV-WR-replicate 3 [RPS20_KI_8hpi_3] |
|
| Relations |
| BioProject |
PRJNA695555 |
| SRA |
SRP303696 |
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