Housekeeping U1 snRNA facilitates antiviral innate immunity by promoting TRIM25-mediated RIG-I activation

被引：4

作者：

Zhang, Fan ^{[1
,2
,3
]}

Liu, Siying ^{[1
,2
]}

Qiao, Zigang ^{[1
,2
]}

Li, Liang ^{[1
,2
]}

Han, Yu ^{[1
,2
]}

Sun, Jiya ^{[1
,2
]}

Ge, Chenglong ^{[4
]}

Zhu, Jingfei ^{[1
,2
]}

Li, Dapei ^{[1
,2
]}

Yao, Haiping ^{[1
,2
]}

Zhang, Huiying ^{[1
,2
]}

Dai, Jianfeng ^{[5
]}

Yan, Yongdong ^{[6
]}

Chen, Zhengrong ^{[6
]}

Yin, Lichen ^{[2
,4
]}

Ma, Feng ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Suzhou Inst Syst Med, Natl Key Lab Immun & Inflammat, Suzhou 215123, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Suzhou Inst Syst Med, CAMS Key Lab Synthet Biol Regulatory Elements, Suzhou 215123, Peoples R China

[3] Xi An Jiao Tong Univ, Sch Pharm, Xian 710061, Peoples R China

[4] Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Collaborat Innovat Ctr Suzhou Nano Sci & Technol, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Suzhou 215123, Peoples R China

[5] Soochow Univ, Inst Biol & Med Sci, Suzhou 215123, Peoples R China

[6] Soochow Univ, Childrens Hosp, Dept Resp Med, Suzhou 215025, Peoples R China

来源：

CELL REPORTS | 2024年 / 43卷 / 03期

基金：

中国国家自然科学基金;

关键词：

SMALL NUCLEAR RNAS; E3 UBIQUITIN LIGASE; NONCODING RNA; INTERFERON; RECOGNITION; RESPONSES; COMPLEX; SENSORS; TRIGGER; BODIES;

D O I：

10.1016/j.celrep.2024.113945

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164 -nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non -coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18 , a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden in vitro and in vivo . Knockout of RNVU1-18 is sufficient to impair the type I interferon -dependent antiviral innate immunity. U1 snRNA is required to fully activate the retinoic acid -inducible gene I (RIG -I) -dependent antiviral signaling, since it interacts with tripartite motif 25 (TRIM25) and enhances the RIG-I-TRIM25 interaction to trigger K63 -linked ubiquitination of RIG -I. Our study reveals the important role of housekeeping U1 snRNA in regulating host antiviral innate immunity and restricting RNA virus infection.

引用

页数：21

共 65 条

[1] Global estimates of excess deaths from COVID-19 [J].

Acosta, Enrique .

NATURE, 2023, 613 (7942) :31-33

[2] U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer's disease [J].

Bai, Bing ;

Hales, Chadwick M. ;

Chen, Ping-Chung ;

Gozal, Yair ;

Dammer, Eric B. ;

Fritz, Jason J. ;

Wang, Xusheng ;

Xia, Qiangwei ;

Duong, Duc M. ;

Street, Craig ;

Cantero, Gloria ;

Cheng, Dongmei ;

Jones, Drew R. ;

Wu, Zhiping ;

Li, Yuxin ;

Diner, Ian ;

Heilman, Craig J. ;

Rees, Howard D. ;

Wu, Hao ;

Lin, Li ;

Szulwach, Keith E. ;

Gearing, Marla ;

Mufson, Elliott J. ;

Bennett, David A. ;

Montine, Thomas J. ;

Seyfried, Nicholas T. ;

Wingo, Thomas S. ;

Sun, Yi E. ;

Jin, Peng ;

Hanfelt, John ;

Willcock, Donna M. ;

Levey, Allan ;

Lah, James J. ;

Peng, Junmin .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (41) :16562-16567

[3] Nucleic Acid Recognition by the Innate Immune System [J].

Barbalat, Roman ;

Ewald, Sarah E. ;

Mouchess, Maria L. ;

Barton, Gregory M. .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :185-214

[4] Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids [J].

Bartok, Eva ;

Hartmann, Gunther .

IMMUNITY, 2020, 53 (01) :54-77

[5] U1 snRNP Determines mRNA Length and Regulates Isoform Expression [J].

Berg, Michael G. ;

Singh, Larry N. ;

Younis, Ihab ;

Liu, Qiang ;

Pinto, Anna Maria ;

Kaida, Daisuke ;

Zhang, Zhenxi ;

Cho, Sungchan ;

Sherrill-Mix, Scott ;

Wan, Lili ;

Dreyfuss, Gideon .

CELL, 2012, 150 (01) :53-64

[6] Ultraviolet radiation damages self noncoding RNA and is detected by TLR3 [J].

Bernard, Jamie J. ;

Cowing-Zitron, Christopher ;

Nakatsuji, Teruaki ;

Muehleisen, Beda ;

Muto, Jun ;

Borkowski, Andrew W. ;

Martinez, Laisel ;

Greidinger, Eric L. ;

Yu, Benjamin D. ;

Gallo, Richard L. .

NATURE MEDICINE, 2012, 18 (08) :1286-+

[7] Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer [J].

Bowling, Elizabeth A. ;

Wang, Jarey H. ;

Gong, Fade ;

Wu, William ;

Neill, Nicholas J. ;

Kim, Ik Sun ;

Tyagi, Siddhartha ;

Orellana, Mayra ;

Kurley, Sarah J. ;

Dominguez-Vidana, Rocio ;

Chung, Hsiang-Ching ;

Hsu, Tiffany Y-T ;

Dubrulle, Julien ;

Saltzman, Alexander B. ;

Li, Heyuan ;

Meena, Jitendra K. ;

Canlas, Gino M. ;

Chamakuri, Srinivas ;

Singh, Swarnima ;

Simon, Lukas M. ;

Olson, Calla M. ;

Dobrolecki, Lacey E. ;

Lewis, Michael T. ;

Zhang, Bing ;

Golding, Ido ;

Rosen, Jeffrey M. ;

Young, Damian W. ;

Malovannaya, Anna ;

Stossi, Fabio ;

Miles, George ;

Ellis, Matthew J. ;

Yu, Lihua ;

Buonamici, Silvia ;

Lin, Charles Y. ;

Karlin, Kristen L. ;

Zhang, Xiang H-F ;

Westbrook, Thomas F. .

CELL, 2021, 184 (02) :384-+

[8] Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity [J].

Chiang, Jessica J. ;

Sparrer, Konstantin M. J. ;

van Gent, Michiel ;

Laessig, Charlotte ;

Huang, Teng ;

Osterrieder, Nikolaus ;

Hopfner, Karl-Peter ;

Gack, Michaela U. .

NATURE IMMUNOLOGY, 2018, 19 (01) :53-+

[9] TRIM25 and its emerging RNA-binding roles in antiviral defense [J].

Choudhury, Nila Roy ;

Heikel, Gregory ;

Michlewski, Gracjan .

WILEY INTERDISCIPLINARY REVIEWS-RNA, 2020, 11 (04)

[10] RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination [J].

Choudhury, Nila Roy ;

Heikel, Gregory ;

Trubitsyna, Maryia ;

Kubik, Peter ;

Nowak, Jakub Stanislaw ;

Webb, Shaun ;

Granneman, Sander ;

Spanos, Christos ;

Rappsilber, Juri ;

Castello, Alfredo ;

Michlewski, Gracjan .

BMC BIOLOGY, 2017, 15

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