A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration

Troels K H Scheel; Joseph M Luna; Matthias Liniger; Eiko Nishiuchi; Kathryn Rozen-Gagnon; Amir Shlomai; Gaël Auray; Markus Gerber; John Fak; Irene Keller; Rémy Bruggmann; Robert B Darnell; Nicolas Ruggli; Charles M Rice

doi:10.1016/j.chom.2016.02.007

A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration

Troels K H Scheel, Joseph M Luna, Matthias Liniger, Eiko Nishiuchi, Kathryn Rozen-Gagnon, Amir Shlomai, Gaël Auray, Markus Gerber, John Fak, Irene Keller, Rémy Bruggmann, Robert B Darnell, Nicolas Ruggli, Charles M Rice

65 Citationer (Scopus)

Abstract

Small non-coding RNAs have emerged as key modulators of viral infection. However, with the exception of hepatitis C virus, which requires the liver-specific microRNA (miRNA)-122, the interactions of RNA viruses with host miRNAs remain poorly characterized. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) proteins to characterize strengths and specificities of miRNA interactions in the context of 15 different RNA virus infections, including several clinically relevant pathogens. Notably, replication of pestiviruses, a major threat to milk and meat industries, critically depended on the interaction of cellular miR-17 and let-7 with the viral 3' UTR. Unlike canonical miRNA interactions, miR-17 and let-7 binding enhanced pestivirus translation and RNA stability. miR-17 sequestration by pestiviruses conferred reduced AGO binding and functional de-repression of cellular miR-17 targets, thereby altering the host transcriptome. These findings generalize the concept of RNA virus dependence on cellular miRNAs and connect virus-induced miRNA sequestration to host transcriptome regulation.

Originalsprog	Engelsk
Tidsskrift	Cell Host & Microbe
Vol/bind	19
Udgave nummer	3
Sider (fra-til)	409-23
Antal sider	15
ISSN	1931-3128
DOI	https://doi.org/10.1016/j.chom.2016.02.007
Status	Udgivet - 9 mar. 2016

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10.1016/j.chom.2016.02.007

http://www.cell.com/article/S1931312816300488/pdf

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title = "A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration",

abstract = "Small non-coding RNAs have emerged as key modulators of viral infection. However, with the exception of hepatitis C virus, which requires the liver-specific microRNA (miRNA)-122, the interactions of RNA viruses with host miRNAs remain poorly characterized. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) proteins to characterize strengths and specificities of miRNA interactions in the context of 15 different RNA virus infections, including several clinically relevant pathogens. Notably, replication of pestiviruses, a major threat to milk and meat industries, critically depended on the interaction of cellular miR-17 and let-7 with the viral 3' UTR. Unlike canonical miRNA interactions, miR-17 and let-7 binding enhanced pestivirus translation and RNA stability. miR-17 sequestration by pestiviruses conferred reduced AGO binding and functional de-repression of cellular miR-17 targets, thereby altering the host transcriptome. These findings generalize the concept of RNA virus dependence on cellular miRNAs and connect virus-induced miRNA sequestration to host transcriptome regulation.",

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AU - Scheel, Troels K H

AU - Luna, Joseph M

AU - Liniger, Matthias

AU - Nishiuchi, Eiko

AU - Rozen-Gagnon, Kathryn

AU - Shlomai, Amir

AU - Auray, Gaël

AU - Gerber, Markus

AU - Fak, John

AU - Keller, Irene

AU - Bruggmann, Rémy

AU - Darnell, Robert B

AU - Ruggli, Nicolas

AU - Rice, Charles M

PY - 2016/3/9

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N2 - Small non-coding RNAs have emerged as key modulators of viral infection. However, with the exception of hepatitis C virus, which requires the liver-specific microRNA (miRNA)-122, the interactions of RNA viruses with host miRNAs remain poorly characterized. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) proteins to characterize strengths and specificities of miRNA interactions in the context of 15 different RNA virus infections, including several clinically relevant pathogens. Notably, replication of pestiviruses, a major threat to milk and meat industries, critically depended on the interaction of cellular miR-17 and let-7 with the viral 3' UTR. Unlike canonical miRNA interactions, miR-17 and let-7 binding enhanced pestivirus translation and RNA stability. miR-17 sequestration by pestiviruses conferred reduced AGO binding and functional de-repression of cellular miR-17 targets, thereby altering the host transcriptome. These findings generalize the concept of RNA virus dependence on cellular miRNAs and connect virus-induced miRNA sequestration to host transcriptome regulation.

AB - Small non-coding RNAs have emerged as key modulators of viral infection. However, with the exception of hepatitis C virus, which requires the liver-specific microRNA (miRNA)-122, the interactions of RNA viruses with host miRNAs remain poorly characterized. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) proteins to characterize strengths and specificities of miRNA interactions in the context of 15 different RNA virus infections, including several clinically relevant pathogens. Notably, replication of pestiviruses, a major threat to milk and meat industries, critically depended on the interaction of cellular miR-17 and let-7 with the viral 3' UTR. Unlike canonical miRNA interactions, miR-17 and let-7 binding enhanced pestivirus translation and RNA stability. miR-17 sequestration by pestiviruses conferred reduced AGO binding and functional de-repression of cellular miR-17 targets, thereby altering the host transcriptome. These findings generalize the concept of RNA virus dependence on cellular miRNAs and connect virus-induced miRNA sequestration to host transcriptome regulation.

U2 - 10.1016/j.chom.2016.02.007

DO - 10.1016/j.chom.2016.02.007

M3 - Journal article

C2 - 26962949

SN - 1931-3128

VL - 19

SP - 409

EP - 423

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration

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