RNA Structure and Function
RNA Structure and Function
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RNA结构和功能
DOI：
10.1007/978-3-031-36390-0_6
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bonetti A
中科院分区：
文献类型：
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作者：
Bonetti A
与其他生物大分子不同，RNA有两个主要任务：由其序列决定的信息编码潜力和由其二级和三级结构决定的催化/调节作用。在过去的十年中，生物物理和生化技术的显著进步使研究人员能够开始探索性研究RNA结构与其功能之间的关系。在其他技术改进中，下一代测序(NGS)工具的爆炸性增长使得在转录组范围内研究细胞中的RNA折叠成为可能。对2D和3D结构的深入了解对于理解RNA的作用机制以及设计合成RNA和开发RNA靶向药物是极其重要的。RNA分子可以采用特定的3D基序，这些基序现在被认为是可药物的，并提供了尚未开发的潜力，可以在治疗上调节许多细胞过程，包括那些与“不可药物的”蛋白质靶点有关的过程。在制药领域对RNA目标组的兴趣与日俱增的同时，RNA折叠的计算机模拟正在开发补充方法。目前，RNA结构探测方法只能捕获部分结构信息。直接测量完整的RNA结构的能力有助于研究其功能和调控机制以及可药性。在本章中，我们将总结确定RNA结构/基序的生物物理和生化策略，包括将分子生物学策略与NGS读数相结合的最新方法。
Unlike other large biomolecules, RNA carries two main tasks: an informational coding potential governed by its sequence and a catalytic/regulatory role, determined by its secondary and tertiary structure. During the last decade, a significant improvement in biophysical and biochemical techniques has enabled researchers to initiate exploratory studies on the relationship between RNA structure and its function. Among other technological improvements, the explosion of next generation sequencing (NGS) tools has allowed the transcriptome-wide investigation of RNA folding in cells. Deeper knowledge of 2D and 3D structures is extremely important for understanding the mechanisms of RNA function as well as for designing synthetic RNAs and the development of RNA-targeted drugs. RNA molecules can adopt specific 3D motifs that are now considered druggable and offer untapped potential to therapeutically modulate numerous cellular processes, including those linked to ‘undruggable’ protein targets. In parallel to the growing interest for the RNA targetome in the pharmaceutical sector, the in-silico modelling of RNA folds is developing complementary methods. Currently, RNA structure probing methods can only capture partial structure information. The ability to directly measure intact RNA structures could facilitate investigations of the functions and regulation mechanisms as well as druggability. In this chapter, we will summarize biophysical and biochemical strategies for determining RNA structures/motifs, including latest approaches that combine molecular biology strategies with NGS readouts.