Identification of the viral and cellular microRNA interactomes during SARS-CoV-2 infection
Nicolas Fossat,
Emma A. Lundsgaard,
Rui Costa,
Lizandro R. Rivera-Rangel,
Louise Nielsen,
Lotte S. Mikkelsen,
Santseharay Ramirez,
Jens Bukh,
Troels K.H. Scheel
Affiliations
Nicolas Fossat
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark; Corresponding author
Emma A. Lundsgaard
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Rui Costa
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Lizandro R. Rivera-Rangel
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Louise Nielsen
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Lotte S. Mikkelsen
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Santseharay Ramirez
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Jens Bukh
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Troels K.H. Scheel
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, 2650 Hvidovre and Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, 10065 NY, USA; Corresponding author
Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact worldwide. Mapping virus-host interactions is critical to understand disease progression. MicroRNAs (miRNAs) are important RNA regulators, but their interaction with SARS-CoV-2 RNA was not experimentally investigated. Here, using Argonaute (AGO) cross-linking immunoprecipitation combined with RNA proximity ligation (CLEAR-CLIP), we provide unbiased mapping of SARS-CoV-2/miRNA interactions. We identified six main regions on the viral RNA bound primarily by one specific miRNA. Targeted mutagenesis and AGO1-3 knockdown demonstrated that these interactions are not critical for virus production. Moreover, we identified perturbed regulation of cellular miRNA interactions during infection, including non-compensated viral sequestration of the miR-15 family. Transcriptome analysis further showed that mRNAs targeted by this miRNA family are derepressed. This work delineates the interphase between miRNA regulation and SARS-CoV-2 infection and further contributes to deciphering the full molecular interactome of this virus.
