Abstract
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.
Keywords: COVID-19; HCoV-OC43; LARP1; RNA; RNA interactome capture; RNA-binding proteins; SARS-CoV-2; coronavirus; mass spectrometry; virus.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, mass spectrometry, HCoV-OC43, RNA, RNA-binding proteins, virus., LARP1, RNA interactome capture, 【초록키워드】 Transcriptome, mass spectrometry, protocol, Antiviral, HCoV-OC43, virus, RNAs, Replication, Protein, pathogen, mRNA, HCoV, pathway, experiment, RNA virus, OC43, host proteins, Interaction, mTOR, LARP1, ZC3HAV1, ribonucleoprotein, life cycle, Factor, therapeutic interventions, knockdown, Coronaviral, TRIM25, downstream, mTOR signaling, Host, robust, CSDE1, EIF3D, PARP12, SHFL, responsible, identify, develop, conserved, provide, analysis, interact, evade, Applying, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2 RNA,