Influenza virus infection causes global RNAPII termination defects
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Burgos (UBU) |
| Repositorio: | Repositorio Institucional de la Universidad de Burgos (RIUBU) |
| OAI Identifier: | oai:riubu.ubu.es:10259/10919 |
| Acceso en línea: | https://hdl.handle.net/10259/10919 |
| Access Level: | acceso abierto |
| Palabra clave: | Virus Poli ADP ribosa polimerasa NAD-ADP-ribosyltransferase |
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Influenza virus infection causes global RNAPII termination defectsZhao, NanSebastiano, VittorioMoshkina, NatashaMena, NachoHultquist, JuddJimenez-Morales, DavidMa, YixuanRialdi, AlexAlbrecht, RandyFenouil, RomainSánchez-Aparicio, M. T.Ayllón Barasoain, JuanRavisankar, SwetaHaddad, BaharehHo, Sook-YiunLow, DianaJin, JianYurchenko, VyacheslavPrinjha, Rab K.Tarakhovsky, AlexanderSquatrito, MassimoPinto, DalilaKimaada, AlletteByun, MinjiSmith, Melissa LairdSebra, RobertGuccione, ErnestoTumpey, TerrenceKrogan, NevanGreenbaum, Benjaminvan Bakel, HarmGarcía Sastre, AdolfoMarazzi, IvanVirusPoli ADP ribosa polimerasaNAD-ADP-ribosyltransferaseViral 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.We thank all members of the laboratories of I.M. and A.G.-S., and J. Bloom and A. Kornblihtt for valuable discussions and suggestions on the manuscript. We thank the Medicinal Chemistry Core, Integrated Screening Core, Microscopy CoRE,, and Global Health and Emerging Pathogens Institute (GHEPI) at the Icahn School of Medicine at Mount Sinai. H.v.B., I.M., and A.G.-S. are partially supported by HHSN272201400008C–Center for Research on Influenza Pathogenesis (CRIP), a NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS). I.M. is supported in part by the Department of Defense W911NF-14-1-0353. I.M. and H.v.B. are supported by NIH grant 1R01AN3663134. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai.Nature Research202520252018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/10259/10919reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)instname:Universidad de Burgos (UBU)InglésNature Structural and Molecular Biology. 2018, V. 25, n. 9, p. 885-893https://doi.org/10.1038/s41594-018-0124-7info:eu-repo/semantics/openAccessoai:riubu.ubu.es:10259/109192026-05-28T07:56:11Z |
| dc.title.none.fl_str_mv |
Influenza virus infection causes global RNAPII termination defects |
| title |
Influenza virus infection causes global RNAPII termination defects |
| spellingShingle |
Influenza virus infection causes global RNAPII termination defects Zhao, Nan Virus Poli ADP ribosa polimerasa NAD-ADP-ribosyltransferase |
| title_short |
Influenza virus infection causes global RNAPII termination defects |
| title_full |
Influenza virus infection causes global RNAPII termination defects |
| title_fullStr |
Influenza virus infection causes global RNAPII termination defects |
| title_full_unstemmed |
Influenza virus infection causes global RNAPII termination defects |
| title_sort |
Influenza virus infection causes global RNAPII termination defects |
| dc.creator.none.fl_str_mv |
Zhao, Nan Sebastiano, Vittorio Moshkina, Natasha Mena, Nacho Hultquist, Judd Jimenez-Morales, David Ma, Yixuan Rialdi, Alex Albrecht, Randy Fenouil, Romain Sánchez-Aparicio, M. T. Ayllón Barasoain, Juan Ravisankar, Sweta Haddad, Bahareh Ho, Sook-Yiun Low, Diana Jin, Jian Yurchenko, Vyacheslav Prinjha, Rab K. Tarakhovsky, Alexander Squatrito, Massimo Pinto, Dalila Kimaada, Allette Byun, Minji Smith, Melissa Laird Sebra, Robert Guccione, Ernesto Tumpey, Terrence Krogan, Nevan Greenbaum, Benjamin van Bakel, Harm García Sastre, Adolfo Marazzi, Ivan |
| author |
Zhao, Nan |
| author_facet |
Zhao, Nan Sebastiano, Vittorio Moshkina, Natasha Mena, Nacho Hultquist, Judd Jimenez-Morales, David Ma, Yixuan Rialdi, Alex Albrecht, Randy Fenouil, Romain Sánchez-Aparicio, M. T. Ayllón Barasoain, Juan Ravisankar, Sweta Haddad, Bahareh Ho, Sook-Yiun Low, Diana Jin, Jian Yurchenko, Vyacheslav Prinjha, Rab K. Tarakhovsky, Alexander Squatrito, Massimo Pinto, Dalila Kimaada, Allette Byun, Minji Smith, Melissa Laird Sebra, Robert Guccione, Ernesto Tumpey, Terrence Krogan, Nevan Greenbaum, Benjamin van Bakel, Harm García Sastre, Adolfo Marazzi, Ivan |
| author_role |
author |
| author2 |
Sebastiano, Vittorio Moshkina, Natasha Mena, Nacho Hultquist, Judd Jimenez-Morales, David Ma, Yixuan Rialdi, Alex Albrecht, Randy Fenouil, Romain Sánchez-Aparicio, M. T. Ayllón Barasoain, Juan Ravisankar, Sweta Haddad, Bahareh Ho, Sook-Yiun Low, Diana Jin, Jian Yurchenko, Vyacheslav Prinjha, Rab K. Tarakhovsky, Alexander Squatrito, Massimo Pinto, Dalila Kimaada, Allette Byun, Minji Smith, Melissa Laird Sebra, Robert Guccione, Ernesto Tumpey, Terrence Krogan, Nevan Greenbaum, Benjamin van Bakel, Harm García Sastre, Adolfo Marazzi, Ivan |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Virus Poli ADP ribosa polimerasa NAD-ADP-ribosyltransferase |
| topic |
Virus Poli ADP ribosa polimerasa NAD-ADP-ribosyltransferase |
| description |
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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10259/10919 |
| url |
https://hdl.handle.net/10259/10919 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Nature Structural and Molecular Biology. 2018, V. 25, n. 9, p. 885-893 https://doi.org/10.1038/s41594-018-0124-7 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Research |
| publisher.none.fl_str_mv |
Nature Research |
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reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU) instname:Universidad de Burgos (UBU) |
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Universidad de Burgos (UBU) |
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Repositorio Institucional de la Universidad de Burgos (RIUBU) |
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Repositorio Institucional de la Universidad de Burgos (RIUBU) |
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