TY - JOUR
T1 - Influenza Virus Mounts a Two-Pronged Attack on Host RNA Polymerase II Transcription
AU - Bauer, David L.V.
AU - Tellier, Michael
AU - Martínez-Alonso, Mónica
AU - Nojima, Takayuki
AU - Proudfoot, Nick J.
AU - Murphy, Shona
AU - Fodor, Ervin
N1 - Funding Information:
We thank Wendy Barclay, Rebecca Frise, and Marian Killip for providing viruses and Steven West for providing cell lines. We thank Joan Steitz and Lars Dölken for helpful discussions, comments, and sharing data before publication. We are also grateful to Justyna Zaborowska, Kinga Kamieniarz-Gdula, and the E.F., N.J.P., and S.M. labs for helpful advice. This work was funded by Medical Research Council (MRC) programme grant MR/K000241/1 (to E.F.), an EPA Cephalosporin Junior Research Fellowship (to D.L.V.B.), and a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme PIEF-GA-2012-32§8746 (to M.M.-A.). This work was also supported by European Research Council advanced grant 339270 (to N.J.P.) and Wellcome Trust Investigator awards 107928/Z/15/Z (to N.J.P.) and WT106134A (to S.M.). We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant 090532/Z/09/Z) for the generation of the sequencing data.
Funding Information:
We thank Wendy Barclay, Rebecca Frise, and Marian Killip for providing viruses and Steven West for providing cell lines. We thank Joan Steitz and Lars Dölken for helpful discussions, comments, and sharing data before publication. We are also grateful to Justyna Zaborowska, Kinga Kamieniarz-Gdula, and the E.F., N.J.P., and S.M. labs for helpful advice. This work was funded by Medical Research Council ( MRC ) programme grant MR/K000241/1 (to E.F.), an EPA Cephalosporin Junior Research Fellowship (to D.L.V.B.), and a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme PIEF-GA-2012-32§8746 (to M.M.-A.). This work was also supported by European Research Council advanced grant 339270 (to N.J.P.) and Wellcome Trust Investigator awards 107928/Z/15/Z (to N.J.P.) and WT106134A (to S.M.). We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant 090532/Z/09/Z ) for the generation of the sequencing data.
Funding Information:
We thank Wendy Barclay, Rebecca Frise, and Marian Killip for providing viruses and Steven West for providing cell lines. We thank Joan Steitz and Lars D?lken for helpful discussions, comments, and sharing data before publication. We are also grateful to Justyna Zaborowska, Kinga Kamieniarz-Gdula, and the E.F., N.J.P., and S.M. labs for helpful advice. This work was funded by Medical Research Council (MRC) programme grant MR/K000241/1 (to E.F.), an EPA Cephalosporin Junior Research Fellowship (to D.L.V.B.), and a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme PIEF-GA-2012-32?8746 (to M.M.-A.). This work was also supported by European Research Council advanced grant 339270 (to N.J.P.) and Wellcome Trust Investigator awards 107928/Z/15/Z (to N.J.P.) and WT106134A (to S.M.). We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant 090532/Z/09/Z) for the generation of the sequencing data.
Publisher Copyright:
© 2018 The Author(s)
PY - 2018/5/15
Y1 - 2018/5/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2018.04.047
DO - 10.1016/j.celrep.2018.04.047
M3 - Article
C2 - 29768209
AN - SCOPUS:85046877499
SN - 2211-1247
VL - 23
SP - 2119-2129.e3
JO - Cell Reports
JF - Cell Reports
IS - 7
ER -