Graf Johannes, Kretz Markus
Institute of Biochemistry, Genetics and Microbiology, University of Regensburg, Regensburg, Germany.
Bioessays. 2020 Dec;42(12):e2000027. doi: 10.1002/bies.202000027. Epub 2020 Nov 9.
RNAs have emerged as a major target for diagnostics and therapeutics approaches. Regulatory nonprotein-coding RNAs (ncRNAs) in particular display remarkable versatility. They can fold into complex structures and interact with proteins, DNA, and other RNAs, thus modulating activity, localization, or interactome of multi-protein complexes. Thus, ncRNAs confer regulatory plasticity and represent a new layer of regulatory control. Interestingly, long noncoding RNAs (lncRNAs) tend to acquire complex secondary and tertiary structures and their function-in many cases-is dependent on structural conservation rather than primary sequence conservation. Whereas for many proteins, structure and its associated function are closely connected, for lncRNAs, the structural domains that determine functionality and its interactome are still not well understood. Numerous approaches for analyzing the structural configuration of lncRNAs have been developed recently. Here, will provide an overview of major experimental approaches used in the field, and discuss the potential benefit of using combinatorial strategies to analyze lncRNA modes of action based on structural information.
RNA已成为诊断和治疗方法的主要靶点。特别是调控性非蛋白质编码RNA（ncRNA）具有显著的多功能性。它们可以折叠成复杂的结构，并与蛋白质、DNA和其他RNA相互作用，从而调节多蛋白复合物的活性、定位或相互作用组。因此，ncRNA赋予了调控可塑性，并代表了一层新的调控控制。有趣的是，长链非编码RNA（lncRNA）倾向于形成复杂的二级和三级结构，并且在许多情况下，其功能依赖于结构保守性而非一级序列保守性。对于许多蛋白质来说，结构及其相关功能紧密相连，但对于lncRNA，决定其功能及其相互作用组的结构域仍未得到很好的理解。最近已经开发出许多分析lncRNA结构构型的方法。在此，将概述该领域使用的主要实验方法，并讨论基于结构信息使用组合策略分析lncRNA作用模式的潜在益处。
