• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

SARS-CoV-2 N 蛋白诱导的 Dicer、XPO5、SRSF3 和 hnRNPA3 下调导致肺炎。

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

机构信息

Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing, PR China.

State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, National Center of Technology Innovation for animal model, CAMS & PUMC, Beijing, PR China.

出版信息

Nat Commun. 2024 Aug 13;15(1):6964. doi: 10.1038/s41467-024-51192-1.

DOI:10.1038/s41467-024-51192-1
PMID:39138195
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11322655/
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.

摘要

尽管 RNAi 和 RNA 剪接机制参与调节严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）复制，但它们在 2019 年冠状病毒病（COVID-19）发病机制中的确切作用仍不清楚。在此，我们表明，RNAi 成分（Dicer 和 XPO5）和剪接因子（SRSF3 和 hnRNPA3）表达的降低与 COVID-19 严重程度的增加相关。SARS-CoV-2 N 蛋白诱导 Dicer、XPO5、SRSF3 和 hnRNPA3 的自噬降解，抑制 miRNA 的生物发生和 RNA 剪接，并引发 DNA 损伤、蛋白毒性应激和肺炎。Dicer、XPO5、SRSF3 和 hnRNPA3 的敲低会增加，而过表达则会减少 N 蛋白诱导的肺炎的严重程度。老年小鼠肺组织中 Dicer、XPO5、SRSF3 和 hnRNPA3 的表达水平较低，并且比年轻小鼠更容易发生 N 蛋白诱导的肺炎。多聚（ADP-核糖）聚合酶抑制剂 PJ34 或芳香酶抑制剂阿那曲唑通过恢复 Dicer、XPO5、SRSF3 和 hnRNPA3 的表达来改善 N 蛋白或 SARS-CoV-2 诱导的肺炎。这些发现将有助于开发治疗 SARS-CoV-2 相关肺炎的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/5e6e24459d7c/41467_2024_51192_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/6de27e2c0d0e/41467_2024_51192_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/f9e1ab03a169/41467_2024_51192_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/771d80856a80/41467_2024_51192_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/16756431de20/41467_2024_51192_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/5c9e75f3cda9/41467_2024_51192_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/493254c53d66/41467_2024_51192_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/3605c1654949/41467_2024_51192_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/f308ac0d6a83/41467_2024_51192_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/ceeeb13d66f7/41467_2024_51192_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/5e6e24459d7c/41467_2024_51192_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/6de27e2c0d0e/41467_2024_51192_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/f9e1ab03a169/41467_2024_51192_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/771d80856a80/41467_2024_51192_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/16756431de20/41467_2024_51192_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/5c9e75f3cda9/41467_2024_51192_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/493254c53d66/41467_2024_51192_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/3605c1654949/41467_2024_51192_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/f308ac0d6a83/41467_2024_51192_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/ceeeb13d66f7/41467_2024_51192_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee4/11322655/5e6e24459d7c/41467_2024_51192_Fig10_HTML.jpg

相似文献

1
SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.SARS-CoV-2 N 蛋白诱导的 Dicer、XPO5、SRSF3 和 hnRNPA3 下调导致肺炎。
Nat Commun. 2024 Aug 13;15(1):6964. doi: 10.1038/s41467-024-51192-1.
2
Genes Involved in miRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection.在 SARS-CoV-2 感染中，参与 miRNA 生物发生的基因未下调。
Viruses. 2023 May 16;15(5):1177. doi: 10.3390/v15051177.
3
Re-evaluation of the roles of DROSHA, Export in 5, and DICER in microRNA biogenesis.对 Drosha、5' 端输出因子及 Dicer 在微小RNA生物合成中作用的重新评估。
Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1881-9. doi: 10.1073/pnas.1602532113. Epub 2016 Mar 14.
4
Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels.XPO5 与 Dicer mRNA、pre-miRNA 和病毒 RNA 之间的结合竞争调节人 Dicer 水平。
Nat Struct Mol Biol. 2011 Mar;18(3):323-7. doi: 10.1038/nsmb.1987. Epub 2011 Feb 6.
5
Influence of genetic polymorphisms in DICER and XPO5 genes on the risk of coronary artery disease and circulating levels of vascular miRNAs.DICER 和 XPO5 基因遗传多态性对冠心病风险及循环血管 miRNA 水平的影响。
Thromb Res. 2019 Aug;180:32-36. doi: 10.1016/j.thromres.2019.05.021. Epub 2019 Jun 3.
6
Genetic variants in microRNA machinery genes are associated [corrected] with idiopathic recurrent pregnancy loss risk.微小RNA机制基因中的遗传变异与特发性复发性流产风险相关[已修正]。
PLoS One. 2014 Apr 25;9(4):e95803. doi: 10.1371/journal.pone.0095803. eCollection 2014.
7
A precursor microRNA in a cancer cell nucleus: get me out of here!癌细胞核中的前体 microRNA：放我出去！
Cell Cycle. 2011 Mar 15;10(6):922-5. doi: 10.4161/cc.10.6.15119.
8
Rescuing Dicer expression in inflamed colon tissues alleviates colitis and prevents colitis-associated tumorigenesis.在炎症结肠组织中恢复 Dicer 的表达可缓解结肠炎并防止结肠炎相关的肿瘤发生。
Theranostics. 2020 Apr 27;10(13):5749-5762. doi: 10.7150/thno.41894. eCollection 2020.
9
Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end-stage renal disease.分析 miRNA 加工机制基因（DROSHA、DICER1、RAN 和 XPO5）变异与终末期肾病的关系。
J Clin Lab Anal. 2020 Dec;34(12):e23520. doi: 10.1002/jcla.23520. Epub 2020 Aug 7.
10
MDA-7/IL-24 regulates the miRNA processing enzyme DICER through downregulation of MITF.MDA-7/IL-24 通过下调 MITF 来调节 miRNA 加工酶 DICER。
Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5687-5692. doi: 10.1073/pnas.1819869116. Epub 2019 Mar 6.

引用本文的文献

1
Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.磷脂酰肌醇-4-磷酸5-激酶1α（PIP5K1α）在哮喘相关生物学过程中的作用：对机制及治疗潜力的见解
J Transl Med. 2025 Sep 2;23(1):978. doi: 10.1186/s12967-025-06997-z.
2
SARS-CoV-2 N protein exerts antitumor effects in NSCLC by inducing DNA damage and augmenting chemotherapeutic sensitivity.严重急性呼吸综合征冠状病毒2（SARS-CoV-2）核蛋白通过诱导DNA损伤和增强化疗敏感性在非小细胞肺癌中发挥抗肿瘤作用。
Med Oncol. 2025 Jun 1;42(7):230. doi: 10.1007/s12032-025-02771-9.
3
Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection: Regulation, association, and therapeutic implications.

本文引用的文献

1
Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex.新冠病毒分离的核衣壳蛋白通过破坏 cGAS-G3BP1 复合物抑制 cGAS-DNA 的识别。
Signal Transduct Target Ther. 2023 Apr 26;8(1):170. doi: 10.1038/s41392-023-01420-9.
2
SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence.SARS-CoV-2 感染通过 CHK1 降解和 53BP1 募集受损，诱导 DNA 损伤，并导致细胞衰老。
Nat Cell Biol. 2023 Apr;25(4):550-564. doi: 10.1038/s41556-023-01096-x. Epub 2023 Mar 9.
3
Hallmarks of aging: An expanding universe.
血管紧张素转换酶2与肝脏严重急性呼吸综合征冠状病毒2感染：调控、关联及治疗意义
World J Gastroenterol. 2025 Feb 14;31(6):100864. doi: 10.3748/wjg.v31.i6.100864.
衰老的特征：一个不断扩大的领域。
Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3.
4
SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D.SARS-CoV-2 通过 Nsp1 介导的下调 NKG2D 的配体来逃避直接 NK 细胞杀伤。
Cell Rep. 2022 Dec 27;41(13):111892. doi: 10.1016/j.celrep.2022.111892. Epub 2022 Dec 12.
5
DNA damage contributes to age-associated differences in SARS-CoV-2 infection.DNA 损伤导致与年龄相关的 SARS-CoV-2 感染差异。
Aging Cell. 2022 Dec;21(12):e13729. doi: 10.1111/acel.13729. Epub 2022 Oct 18.
6
COVID-19 and cellular senescence.COVID-19 与细胞衰老。
Nat Rev Immunol. 2023 Apr;23(4):251-263. doi: 10.1038/s41577-022-00785-2. Epub 2022 Oct 5.
7
A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery.一种强效的中和抗体通过鼻腔给药提供针对 SARS-CoV-2 奥密克戎和德尔塔变异株的保护。
Signal Transduct Target Ther. 2022 Aug 30;7(1):301. doi: 10.1038/s41392-022-01135-3.
8
The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single-cell resolution.单细胞分辨率下的致死性 COVID-19 和特发性肺纤维化的肺血管系统。
Cardiovasc Res. 2023 Mar 31;119(2):520-535. doi: 10.1093/cvr/cvac139.
9
Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation.SARS-CoV-2 核衣壳蛋白在病毒感染、细胞死亡和炎症中的信号机制。
Int J Biol Sci. 2022 Jul 11;18(12):4704-4713. doi: 10.7150/ijbs.72663. eCollection 2022.
10
Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19.敌友难分：自噬溶酶体途径在 SARS-CoV-2 感染与 COVID-19 中的作用。
Int J Biol Sci. 2022 Jul 11;18(12):4690-4703. doi: 10.7150/ijbs.72544. eCollection 2022.