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

doi:10.1016/j.celrep.2023.112282

Identification of the viral and cellular microRNA interactomes during SARS-CoV-2 infection

Cell Rep. 2023 Apr 25;42(4):112282. doi: 10.1016/j.celrep.2023.112282. Epub 2023 Mar 9.

Authors

Nicolas Fossat¹, Emma A Lundsgaard², Rui Costa², Lizandro R Rivera-Rangel², Louise Nielsen², Lotte S Mikkelsen², Santseharay Ramirez², Jens Bukh², Troels K H Scheel³

Affiliations

¹ 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. Electronic address: nfossat@sund.ku.dk.
² 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.
³ 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. Electronic address: tscheel@sund.ku.dk.

Abstract

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.

Keywords: AGO; CLIP; COVID-19; CP: Immunology; CP: Molecular biology; SARS-CoV-2; miR-15; microRNA; post-transcriptional regulation; viral infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Gene Expression Profiling
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA, Viral / genetics
RNA, Viral / metabolism
SARS-CoV-2 / genetics

Substances

MicroRNAs
RNA, Viral
MIRN15 microRNA, human