Influenza virus infection causes global RNAPII termination defects

Nan Zhao; Vittorio Sebastiano; Natasha Moshkina; Nacho Mena; Judd Hultquist; David Jimenez-Morales; Yixuan Ma; Alex Rialdi; Randy Albrecht; Romain Fenouil; Maria Teresa Sánchez-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 García-Sastre; Ivan Marazzi

doi:10.1038/s41594-018-0124-7

Influenza virus infection causes global RNAPII termination defects

Nan Zhao, Vittorio Sebastiano, Natasha Moshkina, Nacho Mena, Judd Hultquist, David Jimenez-Morales, Yixuan Ma, Alex Rialdi, Randy Albrecht, Romain Fenouil, Maria Teresa Sánchez-Aparicio, Juan Ayllon, Sweta Ravisankar, Bahareh Haddad, Jessica Sook Yuin Ho, Diana Low, Jian Jin, Vyacheslav Yurchenko, Rab K. Prinjha, Alexander TarakhovskyMassimo Squatrito, Dalila Pinto, Kimaada Allette, Minji Byun, Melissa Laird Smith, Robert Sebra, Ernesto Guccione, Terrence Tumpey, Nevan Krogan, Benjamin Greenbaum, Harm van Bakel, Adolfo García-Sastre, Ivan Marazzi

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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.

Original language	English
Pages (from-to)	885-893
Number of pages	9
Journal	Nature Structural and Molecular Biology
Volume	25
Issue number	9
DOIs	https://doi.org/10.1038/s41594-018-0124-7
State	Published - 1 Sep 2018

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Zhao, N., Sebastiano, V., Moshkina, N., Mena, N., Hultquist, J., Jimenez-Morales, D., Ma, Y., Rialdi, A., Albrecht, R., Fenouil, R., Sánchez-Aparicio, M. T., Ayllon, J., Ravisankar, S., Haddad, B., Ho, J. S. Y., Low, D., Jin, J., Yurchenko, V., Prinjha, R. K., ... Marazzi, I. (2018). Influenza virus infection causes global RNAPII termination defects. Nature Structural and Molecular Biology, 25(9), 885-893. https://doi.org/10.1038/s41594-018-0124-7

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title = "Influenza virus infection causes global RNAPII termination defects",

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.",

author = "Nan Zhao and Vittorio Sebastiano and Natasha Moshkina and Nacho Mena and Judd Hultquist and David Jimenez-Morales and Yixuan Ma and Alex Rialdi and Randy Albrecht and Romain Fenouil and S{\'a}nchez-Aparicio, {Maria Teresa} and Juan Ayllon and Sweta Ravisankar and Bahareh Haddad and Ho, {Jessica Sook Yuin} and Diana Low and Jian Jin and Vyacheslav Yurchenko and Prinjha, {Rab K.} and Alexander Tarakhovsky and Massimo Squatrito and Dalila Pinto and Kimaada Allette and Minji Byun and Smith, {Melissa Laird} and Robert Sebra and Ernesto Guccione and Terrence Tumpey and Nevan Krogan and Benjamin Greenbaum and {van Bakel}, Harm and Adolfo Garc{\'i}a-Sastre and Ivan Marazzi",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2018",

month = sep,

day = "1",

doi = "10.1038/s41594-018-0124-7",

language = "English",

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Zhao, N, Sebastiano, V, Moshkina, N, Mena, N, Hultquist, J, Jimenez-Morales, D, Ma, Y, Rialdi, A, Albrecht, R, Fenouil, R, Sánchez-Aparicio, MT, Ayllon, J, Ravisankar, S, Haddad, B, Ho, JSY, Low, D, Jin, J, Yurchenko, V, Prinjha, RK, Tarakhovsky, A, Squatrito, M, Pinto, D, Allette, K, Byun, M, Smith, ML, Sebra, R , Guccione, E, Tumpey, T, Krogan, N, Greenbaum, B, van Bakel, H , García-Sastre, A & Marazzi, I 2018, 'Influenza virus infection causes global RNAPII termination defects', Nature Structural and Molecular Biology, vol. 25, no. 9, pp. 885-893. https://doi.org/10.1038/s41594-018-0124-7

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AU - Zhao, Nan

AU - Sebastiano, Vittorio

AU - Moshkina, Natasha

AU - Mena, Nacho

AU - Hultquist, Judd

AU - Jimenez-Morales, David

AU - Ma, Yixuan

AU - Rialdi, Alex

AU - Albrecht, Randy

AU - Fenouil, Romain

AU - Sánchez-Aparicio, Maria Teresa

AU - Ayllon, Juan

AU - Ravisankar, Sweta

AU - Haddad, Bahareh

AU - Ho, Jessica Sook Yuin

AU - Low, Diana

AU - Jin, Jian

AU - Yurchenko, Vyacheslav

AU - Prinjha, Rab K.

AU - Tarakhovsky, Alexander

AU - Squatrito, Massimo

AU - Pinto, Dalila

AU - Allette, Kimaada

AU - Byun, Minji

AU - Smith, Melissa Laird

AU - Sebra, Robert

AU - Guccione, Ernesto

AU - Tumpey, Terrence

AU - Krogan, Nevan

AU - Greenbaum, Benjamin

AU - van Bakel, Harm

AU - García-Sastre, Adolfo

AU - Marazzi, Ivan

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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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U2 - 10.1038/s41594-018-0124-7

DO - 10.1038/s41594-018-0124-7

M3 - Article

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AN - SCOPUS:85053010233

SN - 1545-9993

VL - 25

SP - 885

EP - 893

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 9

ER -

Influenza virus infection causes global RNAPII termination defects

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