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| Status |
Public on Mar 09, 2022 |
| Title |
Discovery and functional interrogation of the virus and host RNA interactome of SARS-CoV-2 proteins [RNA-Seq] |
| Organisms |
Homo sapiens; Chlorocebus sabaeus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Understanding the molecular functions of SARS-CoV-2 proteins is thus imperative to developing effective antiviral treatments. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs. SARS-CoV-2 proteins, NSP8 and NSP12, are found to specifically bind to untranslated regions of the RNA viral genome, with NSP12 additionally binding to all transcription regulatory sequences. This provides evidence for their central roles in replication and transcription. Moreover, we discovered a potential site of NSP12 mediated genome recombination, which could explain the genetic diversity found in coronaviruses. SARS-CoV-2 proteins exogenously expressed in human lung epithelial cells bind to 4,281 unique host RNAs. Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 which upregulates mitochondrial electron transport and N-linked glycosylation proteins. Furthermore, siRNA knockdown of NSP12-targeted proteins in human lung organoid cells demonstrates substantial antiviral effects. Conversely, NSP9 inhibits host gene expression via blocking mRNA export and dampens antiviral inflammation response such as interleukin 1α (IL1α) production. Our extensive viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics.
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| Overall design |
Vero E6 and A549-ACE2 cells were treated with 1µg/ml doxycyline and infected with SARS-CoV-2 at MOI 0.1 and MOI 3, respectively, for 48 hours before treating with Trizol.
BEAS-2B cells were treated with Trizol when 70-90% confluent.
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| Contributor(s) |
Xiang J, Mueller J, Luo E, Yee B, Schafer D, Schmok J, Tan F, Her H, Chen C, Brannan K, Jones K, Park S, Jin W, McVicar R, Kwong E, Le P, Eric K, Vu A, Li Y, Dong K, Tankka A, Song Y, Van Nostrand E, Leibel S, Yeo GW |
| Citation(s) |
35233578, 35313591 |
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| Submission date |
Apr 28, 2021 |
| Last update date |
Mar 31, 2022 |
| Contact name |
Gene Yeo |
| E-mail(s) |
geneyeo@ucsd.edu
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| Organization name |
UCSD
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| Street address |
2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (2) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL28895 |
Illumina NovaSeq 6000 (Chlorocebus sabaeus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE173508 |
Discovery and functional interrogation of the virus and host RNA interactome of SARS-CoV-2 proteins |
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| Relations |
| BioProject |
PRJNA725867 |
| SRA |
SRP316753 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE173507_RAW.tar |
848.2 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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