Identification of the viral and cellular microRNA interactomes during SARS-CoV-2 infection
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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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TY - JOUR
T1 - Identification of the viral and cellular microRNA interactomes during SARS-CoV-2 infection
AU - Fossat, Nicolas
AU - Lundsgaard, Emma A
AU - Costa, Rui
AU - Rivera-Rangel, Lizandro R
AU - Nielsen, Louise
AU - Mikkelsen, Lotte S
AU - Ramirez, Santseharay
AU - Bukh, Jens
AU - Scheel, Troels K H
N1 - Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2023
Y1 - 2023
N2 - 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.
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.
U2 - 10.1016/j.celrep.2023.112282
DO - 10.1016/j.celrep.2023.112282
M3 - Journal article
C2 - 36961814
VL - 42
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 4
M1 - 112282
ER -
ID: 340529506