Key result
A ribonucleoprotein capture protocol identified 109 host factors directly binding to SARS-CoV-2 RNAs, including antiviral factors ZC3HAV1, TRIM25, and PARP12.
Why the study?
SARS-CoV-2 relies on repurposing host RNA-binding proteins to form its own RNA interactome, but these host factor interactions required characterization.
The mapping of the SARS-CoV-2 RNA interactome identifies 109 host RNA-binding proteins that regulate viral replication, revealing novel antiviral and proviral mechanisms that could serve as therapeutic targets.
Hypothesis-generating for host-directed antivirals; animal data leave open human therapeutic translation.
SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.
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Lee et al. (2020) studied SARS-CoV-2 infection. Ribonucleoprotein capture protocol (RAP-MS) vs. Uninfected cells and no-probe controls was evaluated on Identification of host proteins enriched in the SARS-CoV-2 RNA interactome. A ribonucleoprotein capture protocol identified 109 host factors directly binding to SARS-CoV-2 RNAs, including antiviral factors ZC3HAV1, TRIM25, and PARP12.
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