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Published on: December 23, 2020
A potential role for SARS-CoV-2 small viral RNAs in targeting host microRNAs and modulating gene expression
Zachary T Neeb1, Alexander J Ritter2, Lokendra V Chauhan3
1Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California Santa Cruz, Santa Cruz, CA, USA.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19) in humans, with symptoms ranging from mild to severe, including fatality. The molecular mechanisms surrounding the effects of viral infection on the host RNA machinery remain poorly characterized. We used a comparative transcriptomics approach to investigate the effects of SARS-CoV-2 infection on the host mRNA and sRNA expression machinery in a human lung epithelial cell line (Calu-3) and an African green monkey kidney cell line (Vero-E6). Upon infection, we observed global changes in host gene expression and differential expression of dozens of host miRNAs, many with known links to viral infection and immune response. Additionally, we discovered an expanded landscape of more than a hundred SARS-CoV-2-derived small viral RNAs (svRNAs) predicted to interact with differentially expressed host mRNAs and miRNAs. svRNAs are derived from distinct regions of the viral genome and sequence signatures suggest they are produced by a non-canonical biogenesis pathway. 52 of the 67 svRNAs identified in Calu-3 cells are predicted to interact with differentially expressed miRNAs, with many svRNAs having multiple targets. Accordingly, we speculate that these svRNAs may play a role in SARS-CoV-2 propagation by modulating post-transcriptional gene regulation, and that methods for antagonizing them may have therapeutic value.
Insights
This study reveals novel small viral RNAs (svRNAs) produced by SARS-CoV-2 that interact with host gene expression. These svRNAs may influence viral propagation and offer potential therapeutic targets for COVID-19.
Area of Science:
- Molecular Biology
- Virology
- Genomics
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, but its impact on host RNA machinery is unclear.
- Understanding viral-host interactions at the molecular level is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effects of SARS-CoV-2 infection on host mRNA and small RNA (sRNA) expression.
- To identify and characterize SARS-CoV-2-derived small viral RNAs (svRNAs) and their potential interactions with host molecules.
Main Methods:
- Comparative transcriptomics analysis of infected human lung (Calu-3) and monkey kidney (Vero-E6) cell lines.
- Identification and sequencing of host and viral small RNAs.
- Bioinformatic prediction of interactions between svRNAs and host mRNAs/miRNAs.
Main Results:
- SARS-CoV-2 infection caused global changes in host gene expression and differential expression of host microRNAs (miRNAs).
- Over a hundred novel svRNAs were discovered, originating from various viral genome regions via a non-canonical pathway.
- A significant number of svRNAs were predicted to interact with differentially expressed host miRNAs and mRNAs, suggesting a role in post-transcriptional regulation.
Conclusions:
- SARS-CoV-2 infection profoundly alters host gene expression and produces unique svRNAs.
- These svRNAs may modulate host post-transcriptional gene regulation, potentially aiding viral propagation.
- Targeting these svRNAs could represent a novel therapeutic strategy against COVID-19.
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