未剪接HIV-1 RNA的核保留作为潜伏期可逆的转录后阻断

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Agnieszka Dorman, Maryam Bendoumou, Aurelija Valaitienė, Jakub Wadas, Haider Ali, Antoine Dutilleul, Paolo Maiuri, Lorena Nestola, Monika Bociaga-Jasik, Gilbert Mchantaf, Coca Necsoi, Stéphane De Wit, Véronique Avettand-Fenoël, Alessandro Marcello, Krzysztof Pyrc, Alexander O. Pasternak, Carine Van Lint, Anna Kula-Pacurar
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引用次数: 0

摘要

HIV-1的潜伏期主要表现在转录水平上,对转录后机制及其对再激活的贡献知之甚少。病毒蛋白Rev控制非剪接和单剪接RNA的核质输出,这是前病毒复制能力的核心,因此是在“休克-杀死”治疗过程中有效病毒再激活的先决条件。在感染和再激活过程中,未剪接的HIV-1 RNA受到核外泌体Rev辅助因子mat3和MTR4辅助因子的复杂和动态调控。mtr3和MTR4共存于相同的核糖核蛋白复合体中,分别发挥维持或降解RNA的功能,Rev协调这种调节开关。此外,我们提供了来自22名接受art治疗的HIV患者的体外培养物中未剪接HIV-1 RNA的核保留的证据,强调了对病毒RNA核胞质输出的可逆转录后阻断,这与治疗干预措施的设计有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Nuclear retention of unspliced HIV-1 RNA as a reversible post-transcriptional block in latency

Nuclear retention of unspliced HIV-1 RNA as a reversible post-transcriptional block in latency

HIV-1 latency is mainly characterized at transcriptional level, and little is known about post-transcriptional mechanisms and their contribution to reactivation. The viral protein Rev controls the nucleocytoplasmic export of unspliced and singly-spliced RNA that is central to proviral replication-competence and is therefore a prerequisite for efficient viral reactivation during the “shock-and-kill” cure therapy. Here we show that during infection and reactivation, unspliced HIV-1 RNA is a subject to complex and dynamic regulation by the Rev cofactor MATR3 and the MTR4 cofactor of the nuclear exosome. MATR3 and MTR4 coexist in the same ribonucleoprotein complex functioning to either maintain or degrade the RNA, respectively, with Rev orchestrating this regulatory switch. Moreover, we provide evidence of nuclear retention of unspliced HIV-1 RNA in ex vivo cultures from 22 ART-treated people with HIV, highlighting a reversible post-transcriptional block to viral RNA nucleocytoplasmic export that is relevant to the design of curative interventions.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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