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Cell Rep
. 2023 Mar 9;42(4):112282.
doi: 10.1016/j.celrep.2023.112282. Online ahead of print.
Identification of the viral and cellular microRNA interactomes during SARS-CoV-2 infection
Nicolas Fossat 1 , Emma A Lundsgaard 2 , Rui Costa 2 , Lizandro R Rivera-Rangel 2 , Louise Nielsen 2 , Lotte S Mikkelsen 2 , Santseharay Ramirez 2 , Jens Bukh 2 , Troels K H Scheel 3
Affiliations
- PMID: 36961814
- DOI: 10.1016/j.celrep.2023.112282
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.