Huang Yu, Xu Fengwen, Wang Lingwa, Mei Shan, Zhao Fei, Wang Liming, Xie Yu, Wei Liang, Hu Yamei, Gao Zhao, Xue Tiffany, Fang Jugao, Guo Fei
Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
National Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
EMBO Rep. 2025 Aug 18. doi: 10.1038/s44319-025-00551-0.
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.
干扰素（IFN）基因的环状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。在本研究中，我们报告STING通过独立于cGAS和干扰素诱导的机制限制细胞逆转录转座子长散在核元件1（LINE-1）的移动。LINE-1是人类基因组中唯一活跃的自主逆转录转座元件，其转座可导致遗传和自身免疫性疾病。STING对LINE-1的抑制需要其二聚化。从机制上讲，STING与LINE-1 ORF1p相互作用，然后该复合物易位至内质网-高尔基体中间区室（ERGIC）和高尔基体，随后被分选至Rab7阳性溶酶体进行降解。我们的数据揭示了STING通过一种独立于干扰素的机制限制LINE-1逆转录转座来维持宿主基因组完整性的功能。
