hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
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DOI：
10.1038/s41467-020-16168-x
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发表时间：
2020-05-27
影响因子：
16.6
通讯作者：
Millevoi, Stefania
中科院分区：
文献类型：
--
作者：
Herviou, Pauline;Le Bras, Morgane;Millevoi, Stefania
RNA g -四联体（RG4s）是一种控制癌症相关基因mRNA翻译的四链结构。RG4的形成在体外普遍存在，但在细胞中却不存在，这表明存在一种不太明确的分子机制来重塑RG4并保持它们的展开。在这里，我们进行了定量蛋白质组学筛选，以鉴定与典型RG4折叠和未折叠构象相互作用的细胞质蛋白。我们的研究结果确定了hnRNP H/F是调节rg4结构完整性的细胞质机制的重要组成部分，揭示了它们在rg4介导的翻译中的功能，并揭示了影响胶质母细胞瘤结果相关的细胞应激反应的潜在分子机制。RNA g -四联体（RG4s）与癌症基因表达有功能联系。Herviou、Le Bras等人发现了RG4s的蛋白调控机制，揭示了hnRNP H/F和DHX36在rg4介导的翻译调控中影响胶质母细胞瘤癌症治疗的作用和机制。
RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we performed a quantitative proteomic screen to identify cytosolic proteins that interact with a canonical RG4 in its folded and unfolded conformation. Our results identified hnRNP H/F as important components of the cytoplasmic machinery modulating the structural integrity of RG4s, revealed their function in RG4-mediated translation and uncovered the underlying molecular mechanism impacting the cellular stress response linked to the outcome of glioblastoma. RNA G-quadruplexes (RG4s) have been functionally linked to cancer gene expression. Here, Herviou, Le Bras et al. have identified the protein machinery modulating RG4s and reveal the role and mechanism of hnRNP H/F and DHX36 in RG4-mediated translational regulation affecting cancer treatment in glioblastoma.