The SARS-CoV-2 RNA interactome

• DOI: 10.1016/j.molcel.2021.04.022
• Publication Date: 2021-04-27T05:24:26Z
• Authors: Sungyul Lee; Young-suk Lee; Yeon Choi; Ahyeon Son; Youngran Park; Kyung-Min Lee; Jeesoo Kim; Jong-Seo Kim; V. Narry Kim
• Keywords: Interactome; Coronavirus

AbstractSARS-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.