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Cell Rep. 2019 Apr 16;27(3):776-792.e7. doi: 10.1016/j.celrep.2019.03.063.
The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.
Gaucherand L1, Porter BK2, Levene RE1, Price EL2, Schmaling SK3, Rycroft CH4, Kevorkian Y1, McCormick C5, Khaperskyy DA6, Gaglia MM7.
Author information
Abstract
Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression.
Copyright ? 2019 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
CFIm; PA-X; host shutoff; influenza; splicing
PMID: 30995476 DOI: 10.1016/j.celrep.2019.03.063
The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.
Gaucherand L1, Porter BK2, Levene RE1, Price EL2, Schmaling SK3, Rycroft CH4, Kevorkian Y1, McCormick C5, Khaperskyy DA6, Gaglia MM7.
Author information
Abstract
Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression.
Copyright ? 2019 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
CFIm; PA-X; host shutoff; influenza; splicing
PMID: 30995476 DOI: 10.1016/j.celrep.2019.03.063