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

Fan Zhang; Siying Liu; Zigang Qiao; Liang Li; Yu Han; Jiya Sun; Chenglong Ge; Jingfei Zhu; Dapei Li; Haiping Yao; Huiying Zhang; Jianfeng Dai; Yongdong Yan; Zhengrong Chen; Lichen Yin; Feng Ma

doi:10.1016/j.celrep.2024.113945

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

Cell Rep. 2024 Mar 26;43(3):113945. doi: 10.1016/j.celrep.2024.113945. Epub 2024 Mar 13.

Authors

Fan Zhang¹, Siying Liu², Zigang Qiao², Liang Li², Yu Han², Jiya Sun², Chenglong Ge³, Jingfei Zhu², Dapei Li², Haiping Yao², Huiying Zhang², Jianfeng Dai⁴, Yongdong Yan⁵, Zhengrong Chen⁶, Lichen Yin⁷, Feng Ma⁸

Affiliations

¹ National Key Laboratory of Immunity and Inflammation, and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou 215123, China; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
² National Key Laboratory of Immunity and Inflammation, and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou 215123, China.
³ Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.
⁴ Institute of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
⁵ Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou 215025, China.
⁶ Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou 215025, China. Electronic address: chenzhengrong@suda.edu.cn.
⁷ Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China. Electronic address: lcyin@suda.edu.cn.
⁸ National Key Laboratory of Immunity and Inflammation, and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou 215123, China. Electronic address: maf@ism.pumc.edu.cn.

PMID: 38483900
DOI: 10.1016/j.celrep.2024.113945

Abstract

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.

Keywords: CP: Immunology; CP: Molecular biology; RIG-I; TRIM25; U1; antiviral immunity; snRNA; type I interferon.

MeSH terms

DEAD Box Protein 58 / metabolism
Immunity, Innate
RNA, Small Nuclear
Transcription Factors* / metabolism
Tripartite Motif Proteins / metabolism
Ubiquitin-Protein Ligases* / metabolism
Ubiquitination

Substances

U1 small nuclear RNA
Transcription Factors
Ubiquitin-Protein Ligases
DEAD Box Protein 58
RNA, Small Nuclear
Tripartite Motif Proteins