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

David L.V. Bauer, Michael Tellier, Mónica Martínez-Alonso, Takayuki Nojima, Nick J. Proudfoot, Shona Murphy, Ervin Fodor

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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. Bauer et al. investigate the effects of influenza virus infection on host RNA polymerase II (Pol II) transcription genome-wide. They find that infection leads to dysregulation at both the starts and ends of genes. Their work provides insight into both virus-host interactions and fundamental mechanisms of mammalian transcription.

Original languageEnglish
Pages (from-to)2119-2129.e3
JournalCell Reports
Volume23
Issue number7
DOIs
Publication statusPublished - May 15 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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