IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v594y2021i7862d10.1038_s41586-021-03610-3.html
   My bibliography  Save this article

SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis

Author

Listed:
  • Yaara Finkel

    (Weizmann Institute of Science)

  • Avi Gluck

    (Weizmann Institute of Science)

  • Aharon Nachshon

    (Weizmann Institute of Science)

  • Roni Winkler

    (Weizmann Institute of Science)

  • Tal Fisher

    (Weizmann Institute of Science)

  • Batsheva Rozman

    (Weizmann Institute of Science)

  • Orel Mizrahi

    (Weizmann Institute of Science)

  • Yoav Lubelsky

    (Weizmann Institute of Science)

  • Binyamin Zuckerman

    (Weizmann Institute of Science)

  • Boris Slobodin

    (Weizmann Institute of Science)

  • Yfat Yahalom-Ronen

    (Chemical and Environmental Sciences)

  • Hadas Tamir

    (Chemical and Environmental Sciences)

  • Igor Ulitsky

    (Weizmann Institute of Science)

  • Tomer Israely

    (Chemical and Environmental Sciences)

  • Nir Paran

    (Chemical and Environmental Sciences)

  • Michal Schwartz

    (Weizmann Institute of Science)

  • Noam Stern-Ginossar

    (Weizmann Institute of Science)

Abstract

The coronavirus SARS-CoV-2 is the cause of the ongoing pandemic of COVID-191. Coronaviruses have developed a variety of mechanisms to repress host mRNA translation to allow the translation of viral mRNA, and concomitantly block the cellular innate immune response2,3. Although several different proteins of SARS-CoV-2 have previously been implicated in shutting off host expression4–7, a comprehensive picture of the effects of SARS-CoV-2 infection on cellular gene expression is lacking. Here we combine RNA sequencing, ribosome profiling and metabolic labelling of newly synthesized RNA to comprehensively define the mechanisms that are used by SARS-CoV-2 to shut off cellular protein synthesis. We show that infection leads to a global reduction in translation, but that viral transcripts are not preferentially translated. Instead, we find that infection leads to the accelerated degradation of cytosolic cellular mRNAs, which facilitates viral takeover of the mRNA pool in infected cells. We reveal that the translation of transcripts that are induced in response to infection (including innate immune genes) is impaired. We demonstrate this impairment is probably mediated by inhibition of nuclear mRNA export, which prevents newly transcribed cellular mRNA from accessing ribosomes. Overall, our results uncover a multipronged strategy that is used by SARS-CoV-2 to take over the translation machinery and to suppress host defences.

Suggested Citation

  • Yaara Finkel & Avi Gluck & Aharon Nachshon & Roni Winkler & Tal Fisher & Batsheva Rozman & Orel Mizrahi & Yoav Lubelsky & Binyamin Zuckerman & Boris Slobodin & Yfat Yahalom-Ronen & Hadas Tamir & Igor , 2021. "SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis," Nature, Nature, vol. 594(7862), pages 240-245, June.
  • Handle: RePEc:nat:nature:v:594:y:2021:i:7862:d:10.1038_s41586-021-03610-3
    DOI: 10.1038/s41586-021-03610-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03610-3
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-03610-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shufeng Liu & Charles B. Stauft & Prabhuanand Selvaraj & Prabha Chandrasekaran & Felice D’Agnillo & Chao-Kai Chou & Wells W. Wu & Christopher Z. Lien & Clement A. Meseda & Cyntia L. Pedro & Matthew F., 2022. "Intranasal delivery of a rationally attenuated SARS-CoV-2 is immunogenic and protective in Syrian hamsters," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Sara Sunshine & Andreas S. Puschnik & Joseph M. Replogle & Matthew T. Laurie & Jamin Liu & Beth Shoshana Zha & James K. Nuñez & Janie R. Byrum & Aidan H. McMorrow & Matthew B. Frieman & Juliane Winkle, 2023. "Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Matthew J. Cummings & Barnabas Bakamutumaho & Julius J. Lutwama & Nicholas Owor & Xiaoyu Che & Maider Astorkia & Thomas S. Postler & John Kayiwa & Jocelyn Kiconco & Moses Muwanga & Christopher Nsereko, 2024. "COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Catherine F. Hatton & Rachel A. Botting & Maria Emilia Dueñas & Iram J. Haq & Bernard Verdon & Benjamin J. Thompson & Jarmila Stremenova Spegarova & Florian Gothe & Emily Stephenson & Aaron I. Gardner, 2021. "Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Jack S. Gisby & Norzawani B. Buang & Artemis Papadaki & Candice L. Clarke & Talat H. Malik & Nicholas Medjeral-Thomas & Damiola Pinheiro & Paige M. Mortimer & Shanice Lewis & Eleanor Sandhu & Stephen , 2022. "Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    6. Teresa Rummel & Lygeri Sakellaridi & Florian Erhard, 2023. "grandR: a comprehensive package for nucleotide conversion RNA-seq data analysis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Ma’ayan Israeli & Yaara Finkel & Yfat Yahalom-Ronen & Nir Paran & Theodor Chitlaru & Ofir Israeli & Inbar Cohen-Gihon & Moshe Aftalion & Reut Falach & Shahar Rotem & Uri Elia & Ital Nemet & Limor Klik, 2022. "Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:594:y:2021:i:7862:d:10.1038_s41586-021-03610-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.