RT Journal Article SR Electronic T1 The SARS-CoV-2 RNA interactome JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.02.364497 DO 10.1101/2020.11.02.364497 A1 Sungyul Lee A1 Young-suk Lee A1 Yeon Choi A1 Ahyeon Son A1 Youngran Park A1 Kyung-Min Lee A1 Jeesoo Kim A1 Jong-Seo Kim A1 V. Narry Kim YR 2020 UL http://biorxiv.org/content/early/2020/11/02/2020.11.02.364497.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.