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Updated: Sep 29, 2025

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
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Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Published on: December 23, 2020

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Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions

Joy S Xiang1,2, Jasmine R Mueller2, En-Ching Luo2

  • 1Institute of Molecular and Cellular Biology, A*STAR, Singapore.

Research Square
|March 22, 2022
PubMed

Insights

This study maps interactions between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) proteins and viral/host RNAs. Findings reveal viral RNA-binding proteins

Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, involves complex interactions between viral proteins and RNA molecules.
  • Understanding these interactions is crucial for developing effective antiviral strategies.

Approach:

  • Utilized enhanced crosslinking and immunoprecipitation (eCLIP) to map SARS-CoV-2 protein-RNA interactions in infected human lung epithelial cells.
  • Investigated binding preferences of viral proteins to specific regions of the viral genome.
  • Analyzed interactions with host cell coding RNAs and assessed the impact on host gene expression.

Key Points:

  • Specific SARS-CoV-2 proteins (NSP8, NSP12, nucleocapsid) show distinct RNA-binding preferences, implicating them in viral replication, transcription, and packaging.
  • SARS-CoV-2 proteins bind to 4,773 unique host coding RNAs, with some upregulating host gene expression (e.g., NSP12, ORF9c) involved in ER processing and mitochondrial pathways.
  • siRNA knockdown in lung organoids identified potential antiviral host targets across SARS-CoV-2 variants.
  • NSP9 was found to inhibit host gene expression by blocking mRNA export and reducing cytokine production.

Conclusions:

  • The study provides a comprehensive viral protein-RNA interactome for SARS-CoV-2.
  • Identified potential therapeutic targets and elucidated mechanisms contributing to COVID-19 pathogenesis.
  • Offers insights for developing countermeasures against future viral pandemics.

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