HIV-1 蛋白质组与人类宿主 RNA 的相互作用组。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-09-01 Epub Date: 2024-08-09 DOI:10.1038/s44319-024-00222-6

Tinus Schynkel, Willem van Snippenberg, Kimberly Verniers, Gwendolyn M Jang, Nevan J Krogan, Pieter Mestdagh, Linos Vandekerckhove, Wim Trypsteen

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引用次数: 0

摘要

人类免疫缺陷病毒（HIV-1）高度依赖各种宿主因素。据报道，除蛋白质外，宿主 RNA 分子也有助于 HIV-1 的复制和潜伏期的维持。在这里，我们采用原生 RNA 免疫沉淀和测序（nRIPseq）的多种工作流程来确定所有 18 种 HIV-1 （多）蛋白的直接宿主 RNA 相互作用伙伴。我们在 Jurkat 细胞系中确定了 1,727 种 HIV-1 蛋白与人类 RNA 的相互作用，在 SupT1 细胞中确定了 1,558 种蛋白质与人类 RNA 的相互作用，并发现了 HIV-1 似乎在 RNA 水平上使用或控制的独特细胞通路：Tat 与参与超级伸长复合体的蛋白质（AFF1-4、Cyclin-T1）的 mRNA 结合。通过相互作用评分（基于结合丰度）的相关性，我们可以确定置信度最高的相互作用，为此我们进行了小规模的基因敲除筛选，最终确定了三种参与 HIV-1 复制的 HIV-1 蛋白结合 RNA 相互作用因子（AFF2、H4C9 和 RPLP0）。

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Interactome of the HIV-1 proteome and human host RNA.

The human immunodeficiency virus (HIV-1) is highly dependent on a variety of host factors. Beside proteins, host RNA molecules are reported to aid HIV-1 replication and latency maintenance. Here, we implement multiple workflows of native RNA immunoprecipitation and sequencing (nRIPseq) to determine direct host RNA interaction partners of all 18 HIV-1 (poly)proteins. We identify 1,727 HIV-1 protein - human RNA interactions in the Jurkat cell line and 1,558 interactions in SupT1 cells for a subset of proteins, and discover distinct cellular pathways that seem to be used or controlled by HIV-1 on the RNA level: Tat binds mRNAs of proteins involved in the super elongation complex (AFF1-4, Cyclin-T1). Correlation of the interaction scores (based on binding abundancy) allows identifying the highest confidence interactions, for which we perform a small-scale knockdown screen that leads to the identification of three HIV-1 protein binding RNA interactors involved in HIV-1 replication (AFF2, H4C9 and RPLP0).

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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

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.