Influenza Virus Mounts a Two-Pronged Attack on Host RNA Polymerase II Transcription.

Cell Reports
David L V BauerErvin Fodor

Abstract

Influenza virus intimately associates with host RNA polymerase II (Pol II) and mRNA processing machinery. Here, we use mammalian native elongating transcript sequencing (mNET-seq) to examine Pol II behavior during viral infection. We show that influenza virus executes a two-pronged attack on host transcription. First, viral infection causes decreased Pol II gene occupancy downstream of transcription start sites. Second, virus-induced cellular stress leads to a catastrophic failure of Pol II termination at poly(A) sites, with transcription often continuing for tens of kilobases. Defective Pol II termination occurs independently of the ability of the viral NS1 protein to interfere with host mRNA processing. Instead, this termination defect is a common effect of diverse cellular stresses and underlies the production of previously reported downstream-of-gene transcripts (DoGs). Our work has implications for understanding not only host-virus interactions but also fundamental aspects of mammalian transcription.

Citations

Apr 24, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Libin ZhangLiang Bu
Jul 10, 2019·Annual Review of Virology·Thomas P PeacockWendy S Barclay
Mar 5, 2020·Wiley Interdisciplinary Reviews. RNA·Michael TellierShona Murphy
Sep 23, 2020·Nucleic Acids Research·Marion DeclercqSylvie van der Werf
Aug 7, 2020·Molecular Biology of the Cell·Manisha Sharma, Susan R Wente
Sep 5, 2018·Nature Structural & Molecular Biology·Nan ZhaoIvan Marazzi
Jul 28, 2020·Critical Reviews in Microbiology·Chengye LiFanhua Wei
Sep 8, 2018·Viruses·Rachel Emily Levene, Marta Maria Gaglia
May 28, 2020·BMC Bioinformatics·Samuel J RothChristopher Benner
Aug 11, 2020·QJM : Monthly Journal of the Association of Physicians·Claire L Shovlin, Marcela P Vizcaychipi
Feb 6, 2021·Genome Biology·Massimo CavallaroDaniel Hebenstreit
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Dec 24, 2018·Trends in Microbiology·Usama AshrafNadia Naffakh
May 1, 2021·Viruses·Sabrina Weis, Aartjan J W Te Velthuis
Jun 20, 2021·Molecular Cell·Kristina ŽumerPatrick Cramer
Mar 27, 2021·Annual Review of Biochemistry·Tim KrischunsStephen Cusack
Mar 24, 2021·Cold Spring Harbor Perspectives in Biology·Bojana LucicMarina Lusic
Jul 15, 2020·Cold Spring Harbor Perspectives in Medicine·Raquel Muñoz-MorenoAdolfo García-Sastre
Sep 30, 2020·Cold Spring Harbor Perspectives in Medicine·Ecco Staller, Wendy S Barclay

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Datasets Mentioned

BETA
SRP132032

Methods Mentioned

BETA
RNA-seq
FCS
scraping
Illumina sequencing
PCR

Key Resources (RRID) Mentioned

CVCL_0023
CVCL_0421
CVCL_0422

Software Mentioned

cutadapt
Integrative Genomics Viewer ( IGV )
ggplot2
deepTools
hexbin
STAR
R

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