Decrypting noncoding RNA interactions, structures, and functional networks
Decrypting noncoding RNA interactions, structures, and functional networks
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DOI：
10.1101/gr.247239.118
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发表时间：
2019-09-01
期刊：
影响因子：
7
通讯作者：
Calin, George A.
中科院分区：
文献类型：
--
作者：
Fabbri, Muller;Girnita, Leonard;Calin, George A.
非编码RNA(NcRNAs)的世界由数量庞大且不断增长的转录本组成，其长度从几十个碱基到几十个碱基不等，参与所有的生物过程，并在许多类型的人类疾病中表达和/或功能改变。这篇综述的前提是，像许多大型蛋白质一样，ncRNAs具有在空间和功能上组织它们的多结构域结构。随着ncRNA开始被不精确地归类为功能家族，我们在这里综述了它们的结构特性如何影响其功能，重点是结构结构与功能的关系。我们将描述与核酸、蛋白质或脂类直接物理相互作用的“相互作用者元件”(IES)的性质，以及通过二级和/或三级结构的出现指导它们在“ncRNA相互作用者网络”中连接的“结构元件”(Ses)的性质。我们建议将“字母”(ncRNA元件)的光谱组装成“词”(ncRNA结构域)，这些词通过复杂的“句子”(ncRNA相互作用网络)进一步组织成具有功能意义(信号输出)的“短语”(完整的ncRNA结构)。这种符号学类比可以通过IE阻滞剂和/或SE锁定剂的开发来指导ncRNAs作为新的治疗靶点的开发，这些阻断剂和/或SE锁定剂将改变相互作用伙伴的蛋白质、RNA、DNA或脂类的光谱，从而影响疾病的表型。
The world of noncoding RNAs (ncRNAs) is composed of an enormous and growing number of transcripts, ranging in length from tens of bases to tens of kilobases, involved in all biological processes and altered in expression and/or function in many types of human disorders. The premise of this review is the concept that ncRNAs, like many large proteins, have a multidomain architecture that organizes them spatially and functionally. As ncRNAs are beginning to be imprecisely classified into functional families, we review here how their structural properties might inform their functions with focus on structural architecture-function relationships. We will describe the properties of "interactor elements" (IEs) involved in direct physical interaction with nucleic acids, proteins, or lipids and of "structural elements" (SEs) directing their wiring within the "ncRNA interactor networks" through the emergence of secondary and/or tertiary structures. We suggest that spectrums of "letters" (ncRNA elements) are assembled into "words" (ncRNA domains) that are further organized into "phrases" (complete ncRNA structures) with functional meaning (signaling output) through complex "sentences" (the ncRNA interactor networks). This semiotic analogy can guide the exploitation of ncRNAs as new therapeutic targets through the development of IE-blockers and/or SE-lockers that will change the interactor partners' spectrum of proteins, RNAs, DNAs, or lipids and consequently influence disease phenotypes.