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

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, Xinghai Zhang, Sandra Chiu, Xiaozhong Peng (), Ai-Long Huang () and Kai-Fu Tang ()
Additional contact information
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
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
Xiaozhong Peng: National Center of Technology Innovation for animal model, CAMS & PUMC
Ai-Long Huang: Chongqing Medical University
Kai-Fu Tang: Chongqing Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51192-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51192-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51192-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().