E3 ligase SYVN1-mediated polyubiquitination of CPSF6 promotes alternative polyadenylation and antivirus effects of macrophages.

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-02-13 DOI:10.1016/j.celrep.2025.115276

Xin Lu, Chao Liu, Runze Wu, Zhijie Hu, Susu Liu, Xuening Li, Yuchi Liu, Mengxia Li, Jingting Liang, Yingye Huang, Yuting Han, Xin Ou, Ke Deng, Cheng Liang, Shangwu Chen, Yonggui Fu, Anlong Xu

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引用次数: 0

Abstract

Transcriptome-wide alternative polyadenylation (APA) is involved in both innate and adaptive immune responses of immune cells. Downregulation of the CPSF6 protein, one of the 3' end-processing factors, mediates APA in macrophages with responses to virus infection and plays an important role in its anti-virus effect. However, the signaling pathway and molecular mechanism underlying the downregulation of the CPSF6 protein remain elusive. Here, we found that MAVS triggers the nuclear import of the E3 ligase SYVN1 mediated by NUP153 in response to vesicular stomatitis virus infection. Then, SYVN1 catalyzes K48-linked polyubiquitination of CPSF6, resulting in degradation of CPSF6 via the proteasome and then transcriptome-wide APA and anti-virus effects. Our results identify an antiviral mechanism via APA regulation based on ubiquitination modification of the CPSF6 protein, which may serve as a target for developing immune interventions.

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.