通过单分子相关化学探针观察 RNA 结构组合

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in structural biology Pub Date : 2024-07-17 DOI:10.1016/j.sbi.2024.102877
J. Winston Arney , Alain Laederach , Kevin M. Weeks
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引用次数: 0

摘要

RNA 分子通过折叠形成复杂的内部结构。其中许多 RNA 结构具有类似流变特性的集合,每种状态都有不同的功能。直到最近,对 RNA 结构(尤其是细胞内的 RNA 结构)的分析还局限于单一平均结构建模或计算建模的集合建模。这些方法掩盖了许多结构化 RNA 的内在异质性。现在,单分子相关化学探测(smCCP)策略使基于高效执行的化学探测实验测量和解构 RNA 结构集合成为可能。在此,我们概述了单分子探测的基本原理,回顾了当前的集合解卷积策略,并讨论了最近在不同生物系统中的应用。smCCP 为了解生物系统如何利用 RNA 结构的可塑性来应对刺激和改变基因功能带来了一场革命。RNA 集合的能量学通常是微妙的,其中一部分有可能成为调节疾病相关生物过程的目标。
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Visualizing RNA structure ensembles by single-molecule correlated chemical probing

RNA molecules fold to form complex internal structures. Many of these RNA structures populate ensembles with rheostat-like properties, with each state having a distinct function. Until recently, analysis of RNA structures, especially within cells, was limited to modeling either a single averaged structure or computationally-modeled ensembles. These approaches obscure the intrinsic heterogeneity of many structured RNAs. Single-molecule correlated chemical probing (smCCP) strategies are now making it possible to measure and deconvolute RNA structure ensembles based on efficiently executed chemical probing experiments. Here, we provide an overview of fundamental single-molecule probing principles, review current ensemble deconvolution strategies, and discuss recent applications to diverse biological systems. smCCP is enabling a revolution in understanding how the plasticity of RNA structure is exploited in biological systems to respond to stimuli and alter gene function. The energetics of RNA ensembles are often subtle and a subset can likely be targeted to modulate disease-associated biological processes.

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来源期刊
Current opinion in structural biology
Current opinion in structural biology 生物-生化与分子生物学
CiteScore
12.20
自引率
2.90%
发文量
179
审稿时长
6-12 weeks
期刊介绍: Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation
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