Influenza Virus Infection Causes Global RNAPII Termination Defects

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2018 Sep 5

PMID 30177761

Citations 32

Authors

Nan Zhao

Vittorio Sebastiano

Natasha Moshkina

Nacho Mena

Judd Hultquist

David Jimenez-Morales

Yixuan Ma

Alex Rialdi

Randy Albrecht

Romain Fenouil

Maria Teresa Sanchez-Aparicio

Juan Ayllon

Sweta Ravisankar

Bahareh Haddad

Jessica Sook Yuin Ho

Diana Low

Jian Jin

Vyacheslav Yurchenko

Rab K Prinjha

Alexander Tarakhovsky

Massimo Squatrito

Dalila Pinto

Kimaada Allette

Minji Byun

Melissa Laird Smith

Robert Sebra

Ernesto Guccione

Terrence Tumpey

Nevan Krogan

Benjamin Greenbaum

Harm van Bakel

Adolfo Garcia-Sastre

Ivan Marazzi

Affiliations

Soon will be listed here.

Abstract

Viral infection perturbs host cells and can be used to uncover regulatory mechanisms controlling cellular responses and susceptibility to infections. Using cell biological, biochemical, and genetic tools, we reveal that influenza A virus (IAV) infection induces global transcriptional defects at the 3' ends of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions. Deregulated RNAPII leads to expression of aberrant RNAs (3' extensions and host-gene fusions) that ultimately cause global transcriptional downregulation of physiological transcripts, an effect influencing antiviral response and virulence. This phenomenon occurs with multiple strains of IAV, is dependent on influenza NS1 protein, and can be modulated by SUMOylation of an intrinsically disordered region (IDR) of NS1 expressed by the 1918 pandemic IAV strain. Our data identify a strategy used by IAV to suppress host gene expression and indicate that polymorphisms in IDRs of viral proteins can affect the outcome of an infection.

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