LARP7 的液-液相分离抑制了 HIV-1 的复制。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-20 DOI:10.1038/s44319-025-00421-9

Zhuoxin Li, Xiya Fang, Bing Zhao, Ran Liu, Yezhuang Shen, Tingting Li, Yining Wang, Zenglin Guo, Wen Wang, Biyu Zhang, Qiuying Han, Xin Xu, Kai Wang, Libing Yin, Weili Gong, Ailing Li, Tao Zhou, Teng Li, Weihua Li

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引用次数: 0

摘要

HIV-1通过其反激活子Tat启动复制，劫持宿主细胞中的正转录延伸因子b （P-TEFb）。大多数P-TEFb被7SK snRNP维持在无活性状态，直到它被细胞或病毒反激活因子带入转录起始复合物，从而加速转录并促进全长病毒转录物的产生。在这里，我们报道HIV-1感染触发LARP7的液液相分离，LARP7是7SK snRNP的核心成分。它在感染后被纳入hiv -1诱导的LARP7凝析物中。LARP7内在无序区域的保守赖氨酸残基对于其相分离和抑制tat介导的转录都是必不可少的。这些发现确定了一种机制，其中P-TEFb和Tat被隔离在LARP7凝聚物中，抑制HIV-1转录。

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Liquid-liquid phase separation of LARP7 restrains HIV-1 replication.

HIV-1 initiates replication by its transactivator Tat, hijacking the positive transcription elongation factor b (P-TEFb) in the host cell. Most P-TEFb is maintained in an inactive state by 7SK snRNP until it is brought to the transcription initiation complex by cellular or viral transactivators that accelerate transcription and facilitate the production of full-length viral transcripts. Here, we report that HIV-1 infection triggers liquid-liquid phase separation of LARP7, a central component of 7SK snRNP. Tat is incorporated into HIV-1-induced LARP7 condensates after infection. Conserved lysine residues in the intrinsically disordered region of LARP7 are essential for both its phase separation and the inhibition of Tat-mediated transcription. These findings identify a mechanism wherein P-TEFb and Tat are sequestered within LARP7 condensates, restraining HIV-1 transcription.

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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

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