STING inhibits LINE-1 retrotransposition through sorting ORF1p to lysosomes for degradation.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-09-01 Epub Date: 2025-08-18 DOI:10.1038/s44319-025-00551-0

Yu Huang, Fengwen Xu, Lingwa Wang, Shan Mei, Fei Zhao, Liming Wang, Yu Xie, Liang Wei, Yamei Hu, Zhao Gao, Tiffany Xue, Jugao Fang, Fei Guo

{"title":"STING inhibits LINE-1 retrotransposition through sorting ORF1p to lysosomes for degradation.","authors":"Yu Huang, Fengwen Xu, Lingwa Wang, Shan Mei, Fei Zhao, Liming Wang, Yu Xie, Liang Wei, Yamei Hu, Zhao Gao, Tiffany Xue, Jugao Fang, Fei Guo","doi":"10.1038/s44319-025-00551-0","DOIUrl":null,"url":null,"abstract":"<p><p>The cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is known for its critical role in interferon and inflammatory responses. In addition, STING also has functions independent of interferon induction. In this study, we report that STING restricts the mobilization of the cellular retrotransposon long interspersed nuclear element 1 (LINE-1) independent of cGAS and interferon induction. LINE-1 is the only active autonomous retrotransposable element in the human genome and its transposition can cause genetic and autoimmune diseases. STING inhibition of LINE-1 requires its dimerization. Mechanistically, STING interacts with LINE-1 ORF1p, then the complex translocates to the ER-Golgi intermediate compartment (ERGIC) and the Golgi followed by sorting to Rab7-positive lysosomes for degradation. Our data unveil a function of STING in maintaining host genome integrity by restricting LINE-1 retrotransposition via an IFN-independent mechanism.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4607-4630"},"PeriodicalIF":6.2000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457603/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EMBO Reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44319-025-00551-0","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is known for its critical role in interferon and inflammatory responses. In addition, STING also has functions independent of interferon induction. In this study, we report that STING restricts the mobilization of the cellular retrotransposon long interspersed nuclear element 1 (LINE-1) independent of cGAS and interferon induction. LINE-1 is the only active autonomous retrotransposable element in the human genome and its transposition can cause genetic and autoimmune diseases. STING inhibition of LINE-1 requires its dimerization. Mechanistically, STING interacts with LINE-1 ORF1p, then the complex translocates to the ER-Golgi intermediate compartment (ERGIC) and the Golgi followed by sorting to Rab7-positive lysosomes for degradation. Our data unveil a function of STING in maintaining host genome integrity by restricting LINE-1 retrotransposition via an IFN-independent mechanism.

查看原文本刊更多论文

STING通过将ORF1p分类到溶酶体降解来抑制LINE-1反转录转位。

干扰素（IFN）基因的环二核苷酸传感器刺激因子（STING）因其在干扰素和炎症反应中的关键作用而闻名。此外，STING还具有独立于干扰素诱导的功能。在这项研究中，我们报道了STING限制了独立于cGAS和干扰素诱导的细胞反转录转座子long interspersed nuclear element 1 （LINE-1）的动员。LINE-1是人类基因组中唯一活跃的自主反转录因子，其转位可引起遗传和自身免疫性疾病。STING抑制LINE-1需要其二聚化。在机制上，STING与LINE-1 ORF1p相互作用，然后复合物转运到er -高尔基体中间室（ERGIC）和高尔基体，然后分选到rab7阳性溶酶体进行降解。我们的数据揭示了STING通过不依赖于ifn的机制限制LINE-1反转录转位来维持宿主基因组完整性的功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.