Dynamic interactions drive early spliceosome assembly

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology Pub Date : 2024-08-20 DOI:10.1016/j.sbi.2024.102907

Santiago Martínez-Lumbreras , Clara Morguet , Michael Sattler

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引用次数: 0

Abstract

Splicing is a critical processing step during pre-mRNA maturation in eukaryotes. The correct selection of splice sites during the early steps of spliceosome assembly is highly important and crucial for the regulation of alternative splicing. Splice site recognition and alternative splicing depend on cis-regulatory sequence elements in the RNA and trans-acting splicing factors that recognize these elements and crosstalk with the canonical splicing machinery. Structural mechanisms involving early spliceosome complexes are governed by dynamic RNA structures, protein-RNA interactions and conformational flexibility of multidomain RNA binding proteins. Here, we highlight structural studies and integrative structural biology approaches, which provide complementary information from cryo-EM, NMR, small angle scattering, and X-ray crystallography to elucidate mechanisms in the regulation of early spliceosome assembly and quality control, highlighting the role of conformational dynamics.

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动态相互作用推动早期剪接体的组装

剪接是真核生物中前 mRNA 成熟过程中的一个关键处理步骤。在剪接体组装的早期步骤中，正确选择剪接位点非常重要，对替代剪接的调控也至关重要。剪接位点的识别和替代剪接取决于 RNA 中的顺式调控序列元件以及识别这些元件并与典型剪接机制发生串联的反式作用剪接因子。涉及早期剪接体复合物的结构机制受动态 RNA 结构、蛋白质-RNA 相互作用以及多域 RNA 结合蛋白构象灵活性的制约。在此，我们重点介绍结构研究和综合结构生物学方法，这些方法提供了低温电子显微镜、核磁共振、小角散射和 X 射线晶体学的互补信息，以阐明早期剪接体组装和质量控制的调控机制，并强调构象动态的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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