The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.
Cell Rep
; 27(3): 776-792.e7, 2019 04 16.
Article
em En
| MEDLINE
| ID: mdl-30995476
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Proteínas Repressoras
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RNA Mensageiro
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Splicing de RNA
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Proteínas não Estruturais Virais
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article