The SARS-CoV-2 RNA interactome.
SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 ... RNAs. Applying RNP capture on another coronavirus, HCoV-OC43, revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyses and knockdown experiments delineated 17 antiviral RBPs, including ZC3HAV1, TRIM25, PARP12, and SHFL, and 8 proviral RBPs, such as EIF3D and CSDE1, which are responsible for co-opting multiple steps of the mRNA life cycle. This also led to the identification of LARP1, a downstream target of the mTOR signaling pathway, as an antiviral host factor that interacts with the SARS-CoV-2 RNAs. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.
Mesh Terms:
Autoantigens, COVID-19, Coronavirus OC43, Human, HEK293 Cells, Host-Pathogen Interactions, Humans, Protein Binding, Protein Interaction Maps, RNA, Viral, RNA-Binding Proteins, Ribonucleoproteins, SARS-CoV-2, TOR Serine-Threonine Kinases, Transcription Factors, Transcriptome, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Virus Replication
Autoantigens, COVID-19, Coronavirus OC43, Human, HEK293 Cells, Host-Pathogen Interactions, Humans, Protein Binding, Protein Interaction Maps, RNA, Viral, RNA-Binding Proteins, Ribonucleoproteins, SARS-CoV-2, TOR Serine-Threonine Kinases, Transcription Factors, Transcriptome, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Virus Replication
Mol Cell
Date: Jul. 01, 2021
PubMed ID: 33989516
View in: Pubmed Google Scholar
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