UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors

Duomeng Yang (), Tingting Geng, Andrew G. Harrison, Jason G. Cahoon, Jian Xing, Baihai Jiao, Mark Wang, Chao Cheng, Robert E. Hill, Huadong Wang, Anthony T. Vella, Gong Cheng, Yanlin Wang and Penghua Wang ()
Additional contact information
Duomeng Yang: Department of Immunology, School of Medicine, UConn Health
Tingting Geng: Department of Immunology, School of Medicine, UConn Health
Andrew G. Harrison: Department of Immunology, School of Medicine, UConn Health
Jason G. Cahoon: Department of Immunology, School of Medicine, UConn Health
Jian Xing: Department of Neuroscience, School of Medicine, UConn Health
Baihai Jiao: Department of Medicine, School of Medicine, UConn Health
Mark Wang: Department of Immunology, School of Medicine, UConn Health
Chao Cheng: Department of Medicine, Baylor College of Medicine
Robert E. Hill: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital
Huadong Wang: Jinan University
Anthony T. Vella: Department of Immunology, School of Medicine, UConn Health
Gong Cheng: Tsinghua University-Peking University Joint Center for Life Sciences, School of Medicine, Tsinghua University
Yanlin Wang: Department of Medicine, School of Medicine, UConn Health
Penghua Wang: Department of Immunology, School of Medicine, UConn Health

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

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

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45141-1 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_s41467-024-45141-1

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

DOI: 10.1038/s41467-024-45141-1

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 ().