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

Nicolas Fossat, Emma A Lundsgaard, Rui Costa, Lizandro R Rivera-Rangel, Louise Nielsen, Lotte S Mikkelsen, Santseharay Ramirez, Jens Bukh, Troels K H Scheel

Virology

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Article number	112282
Journal	Cell Reports
Volume	42
Issue number	4
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2023.112282
Publication status	Published - 2023

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Identification of the viral and cellular microRNA interactomes during SARS-CoV-2 infection. / Fossat, Nicolas ; Lundsgaard, Emma A ; Costa, Rui ; Rivera-Rangel, Lizandro R; Nielsen, Louise; Mikkelsen, Lotte S; Ramirez, Santseharay ; Bukh, Jens ; Scheel, Troels K H.

In: Cell Reports, Vol. 42, No. 4, 112282, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

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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.",

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AU - Mikkelsen, Lotte S

AU - Ramirez, Santseharay

AU - Bukh, Jens

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AB - 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.

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