{"title":"STING通过将ORF1p分类到溶酶体降解来抑制LINE-1反转录转位。","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":"{\"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}","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
摘要
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。
STING inhibits LINE-1 retrotransposition through sorting ORF1p to lysosomes for degradation.
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.
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.
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