RNA Structures as Mediators of Neurological Diseases and as Drug Targets.
RNA Structures as Mediators of Neurological Diseases and as Drug Targets.
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DOI：
10.1016/j.neuron.2015.06.012
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发表时间：
2015-07-01
期刊：
影响因子：
16.2
通讯作者：
Disney MD
中科院分区：
文献类型：
--
作者：
Bernat V;Disney MD
RNA具有多种折叠结构，这些结构对功能至关重要，因此在细胞生物学中起着关键作用。一个引人注目的例子是核糖体，一个复杂的，三维折叠的大分子机器，协调蛋白质合成。RNA生物化学、结构和分子生物学以及生物信息学的进展揭示了其他非编码RNA，其功能由其结构决定。异常折叠的RNA结构导致疾病并不奇怪。在这篇综述中，我们简要介绍了RNA结构生物学，然后描述了RNA结构如何在细胞中发挥作用，并导致或有助于神经系统疾病。最后，我们强调了合理的设计原则，以提供化学探针和先导化合物靶向结构化RNA的成功应用。基于几个充分表征的RNA驱动的神经系统疾病的例子，我们展示了设计的小分子如何促进RNA功能障碍的研究，阐明RNA在疾病中以前未知的作用，并提供领先的治疗方法。
RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics.