IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51192-1.html
   My bibliography  Save this article

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia

Author

Listed:
  • Yu-Wei Luo

    (Chongqing Medical University)

  • Jiang-Peng Zhou

    (Chongqing Medical University)

  • Hongyu Ji

    (Chongqing Medical University)

  • Doudou Xu

    (National Center of Technology Innovation for animal model, CAMS & PUMC)

  • Anqi Zheng

    (The First Affiliated Hospital of Wenzhou Medical University)

  • Xin Wang

    (Chongqing Medical University)

  • Zhizheng Dai

    (Chongqing Medical University)

  • Zhicheng Luo

    (Chongqing Medical University
    The First Affiliated Hospital of Wenzhou Medical University)

  • Fang Cao

    (Chongqing Medical University)

  • Xing-Yue Wang

    (The First Affiliated Hospital of Wenzhou Medical University)

  • Yunfang Bai

    (Chongqing Medical University)

  • Di Chen

    (Chongqing Medical University)

  • Yueming Chen

    (The First Affiliated Hospital of Wenzhou Medical University)

  • Qi Wang

    (Chongqing Medical University)

  • Yaying Yang

    (Chongqing Medical University)

  • Xinghai Zhang

    (Chinese Academy of Sciences)

  • Sandra Chiu

    (University of Science and Technology of China
    Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases)

  • Xiaozhong Peng

    (National Center of Technology Innovation for animal model, CAMS & PUMC
    School of Basic Medicine Peking Union Medical College)

  • Ai-Long Huang

    (Chongqing Medical University)

  • Kai-Fu Tang

    (Chongqing Medical University)

Abstract

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Suggested Citation

  • Yu-Wei Luo & Jiang-Peng Zhou & Hongyu Ji & Doudou Xu & Anqi Zheng & Xin Wang & Zhizheng Dai & Zhicheng Luo & Fang Cao & Xing-Yue Wang & Yunfang Bai & Di Chen & Yueming Chen & Qi Wang & Yaying Yang & X, 2024. "SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51192-1
    DOI: 10.1038/s41467-024-51192-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51192-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51192-1?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
    ---><---

    References listed on IDEAS

    as
    1. Kenneth H. Dinnon & Sarah R. Leist & Alexandra Schäfer & Caitlin E. Edwards & David R. Martinez & Stephanie A. Montgomery & Ande West & Boyd L. Yount & Yixuan J. Hou & Lily E. Adams & Kendra L. Gully , 2020. "A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures," Nature, Nature, vol. 586(7830), pages 560-566, October.
    2. Elizabeth J. Williamson & Alex J. Walker & Krishnan Bhaskaran & Seb Bacon & Chris Bates & Caroline E. Morton & Helen J. Curtis & Amir Mehrkar & David Evans & Peter Inglesby & Jonathan Cockburn & Helen, 2020. "Factors associated with COVID-19-related death using OpenSAFELY," Nature, Nature, vol. 584(7821), pages 430-436, August.
    3. Björn Schumacher & Joris Pothof & Jan Vijg & Jan H. J. Hoeijmakers, 2021. "The central role of DNA damage in the ageing process," Nature, Nature, vol. 592(7856), pages 695-703, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Dennis Lapuente & Jana Fuchs & Jonas Willar & Ana Vieira Antão & Valentina Eberlein & Nadja Uhlig & Leila Issmail & Anna Schmidt & Friederike Oltmanns & Antonia Sophia Peter & Sandra Mueller-Schmucker, 2021. "Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Brandily, Paul & Brébion, Clément & Briole, Simon & Khoury, Laura, 2021. "A poorly understood disease? The impact of COVID-19 on the income gradient in mortality over the course of the pandemic," European Economic Review, Elsevier, vol. 140(C).
    3. Diana A. Llerena Schiffmacher & Shun-Hsiao Lee & Katarzyna W. Kliza & Arjan F. Theil & Masaki Akita & Angela Helfricht & Karel Bezstarosti & Camila Gonzalo-Hansen & Haico Attikum & Matty Verlaan-de Vr, 2024. "The small CRL4CSA ubiquitin ligase component DDA1 regulates transcription-coupled repair dynamics," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Borau, Sylvie & Couprie, Hélène & Hopfensitz, Astrid, 2022. "The prosociality of married people: Evidence from a large multinational sample," Journal of Economic Psychology, Elsevier, vol. 92(C).
    5. Matthew R. Chang & Luke Tomasovic & Natalia A. Kuzmina & Adam J. Ronk & Patrick O. Byrne & Rebecca Johnson & Nadia Storm & Eduardo Olmedillas & Yixuan J. Hou & Alexandra Schäfer & Sarah R. Leist & Lon, 2022. "IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Anna Adamecz-Völgyi & Ágnes Szabó-Morvai, 2021. "Confidence in public institutions is critical in containing the COVID-19 pandemic," CERS-IE WORKING PAPERS 2126, Institute of Economics, Centre for Economic and Regional Studies.
    7. Shelly J. Robertson & Olivia Bedard & Kristin L. McNally & Carl Shaia & Chad S. Clancy & Matthew Lewis & Rebecca M. Broeckel & Abhilash I. Chiramel & Jeffrey G. Shannon & Gail L. Sturdevant & Rebecca , 2023. "Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Dorn, Florian & Lange, Berit & Braml, Martin & Gstrein, David & Nyirenda, John L.Z. & Vanella, Patrizio & Winter, Joachim & Fuest, Clemens & Krause, Gérard, 2023. "The challenge of estimating the direct and indirect effects of COVID-19 interventions – Toward an integrated economic and epidemiological approach," Economics & Human Biology, Elsevier, vol. 49(C).
    9. Galván, Antonio & Haas, Jannik & Moreno-Leiva, Simón & Osorio-Aravena, Juan Carlos & Nowak, Wolfgang & Palma-Benke, Rodrigo & Breyer, Christian, 2022. "Exporting sunshine: Planning South America’s electricity transition with green hydrogen," Applied Energy, Elsevier, vol. 325(C).
    10. Mahdi Moqri & Andrea Cipriano & Daniel J. Simpson & Sajede Rasouli & Tara Murty & Tineke Anna Jong & Daniel Nachun & Guilherme Sena Brandine & Kejun Ying & Andrei Tarkhov & Karolina A. Aberg & Edwin O, 2024. "PRC2-AgeIndex as a universal biomarker of aging and rejuvenation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. McKee, Martin & Altmann, Danny & Costello, Anthony & Friston, Karl & Haque, Zubaida & Khunti, Kamlesh & Michie, Susan & Oni, Tolullah & Pagel, Christina & Pillay, Deenan & Reicher, Steve & Salisbury, , 2022. "Open science communication: The first year of the UK's Independent Scientific Advisory Group for Emergencies," Health Policy, Elsevier, vol. 126(3), pages 234-244.
    12. João Faro-Viana & Marie-Louise Bergman & Lígia A. Gonçalves & Nádia Duarte & Teresa P. Coutinho & Patrícia C. Borges & Christian Diwo & Rute Castro & Paula Matoso & Vanessa Malheiro & Ana Brennand & L, 2022. "Population homogeneity for the antibody response to COVID-19 BNT162b2/Comirnaty vaccine is only reached after the second dose across all adult age ranges," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    13. Martin S. Eichenbaum & Sergio Rebelo & Mathias Trabandt, 2022. "Inequality in Life and Death," IMF Economic Review, Palgrave Macmillan;International Monetary Fund, vol. 70(1), pages 68-104, March.
    14. Denis Mongin & Nils Bürgisser & Gustavo Laurie & Guillaume Schimmel & Diem-Lan Vu & Stephane Cullati & Delphine Sophie Courvoisier, 2023. "Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    15. Pedro Weickert & Hao-Yi Li & Maximilian J. Götz & Sophie Dürauer & Denitsa Yaneva & Shubo Zhao & Jacqueline Cordes & Aleida C. Acampora & Ignasi Forne & Axel Imhof & Julian Stingele, 2023. "SPRTN patient variants cause global-genome DNA-protein crosslink repair defects," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Pradeep Ramalingam & Michael C. Gutkin & Michael G. Poulos & Taylor Tillery & Chelsea Doughty & Agatha Winiarski & Ana G. Freire & Shahin Rafii & David Redmond & Jason M. Butler, 2023. "Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. Qinghong Fan & Jingrong Shi & Yanhong Yang & Guofang Tang & Mengling Jiang & Jiaojiao Li & Jingyan Tang & Lu Li & Xueliang Wen & Lieguang Zhang & Xizi Deng & Yaping Wang & Yun Lan & Liya Li & Ping Pen, 2022. "Clinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    18. Sakino Shinokawa & Hiroki Abe & Risa Takashima & Ryuta Onishi & Michiyo Hirano, 2023. "Verification of the Effectiveness of a Communication Application in Improving Social Connectedness and Physical Health among Unacquainted Older Men: A Mixed-Methods Pilot Study," IJERPH, MDPI, vol. 20(3), pages 1-15, January.
    19. Raveen Rathnasinghe & Sonia Jangra & Chengjin Ye & Anastasija Cupic & Gagandeep Singh & Carles Martínez-Romero & Lubbertus C. F. Mulder & Thomas Kehrer & Soner Yildiz & Angela Choi & Stephen T. Yeung , 2022. "Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Davida S. Smyth & Monica Trujillo & Devon A. Gregory & Kristen Cheung & Anna Gao & Maddie Graham & Yue Guan & Caitlyn Guldenpfennig & Irene Hoxie & Sherin Kannoly & Nanami Kubota & Terri D. Lyddon & M, 2022. "Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater," Nature Communications, Nature, vol. 13(1), pages 1-9, 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:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51192-1. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.