IGF2BP1 通过与 CCN1 3'UTR 中的 G-四链结构特异性结合来调节 CCN1 的表达。

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biochemistry Biochemistry Pub Date : 2024-09-03 Epub Date: 2024-08-12 DOI:10.1021/acs.biochem.4c00172
Priya Rana, Rajat Ujjainiya, Vishal Bharti, Souvik Maiti, Mary K Ekka
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引用次数: 0

摘要

基因表达的复杂调控是高等生物复杂性的基础,主要由转录和转录后机制控制。mRNA 的 3'- 非翻译区(3'UTR)含有丰富的顺式调控元件,如 G-四叠体(G4s),在转录后调控中起着至关重要的作用。G4s 已成为重要的基因调控因子,影响着 mRNA 的稳定性、翻译和定位。在本研究中,我们研究了位于 CCN1 mRNA 3'UTR 中的一个强大的平行 G4 结构在转录后调控中的作用。这个 G4 结构位于人类 CCN1 停止密码子的近端,在进化上是保守的。我们阐明了它与胰岛素样生长因子 2 结合蛋白 1(IGF2BP1)的相互作用,IGF2BP1 是一种非经典 RNA N6-甲基腺苷(m6A)修饰阅读器,揭示了 RNA 修饰与 G 型四倍体结构之间的新型相互作用。基因敲除实验和诱变研究证明,IGF2BP1 能与 G4 结构特异性结合,从而调节 CCN1 mRNA 的稳定性。此外,我们还揭示了 IGF2BP1 的 RNA 识别基序在 G4 识别中的作用,强调了这种热驱动的相互作用。我们的发现为 G4 RNA 二级结构介导的转录后基因调控的复杂机制提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

IGF2BP1-Mediated Regulation of CCN1 Expression by Specific Binding to G-Quadruplex Structure in Its 3'UTR.

IGF2BP1-Mediated Regulation of CCN1 Expression by Specific Binding to G-Quadruplex Structure in Its 3'UTR.

The intricate regulation of gene expression is fundamental to the biological complexity of higher organisms, and is primarily governed by transcriptional and post-transcriptional mechanisms. The 3'-untranslated region (3'UTR) of mRNA is rich in cis-regulatory elements like G-quadruplexes (G4s), and plays a crucial role in post-transcriptional regulation. G4s have emerged as significant gene regulators, impacting mRNA stability, translation, and localization. In this study, we investigate the role of a robust parallel G4 structure situated within the 3'UTR of CCN1 mRNA in post-transcriptional regulation. This G4 structure is proximal to the stop codon of human CCN1, and evolutionarily conserved. We elucidated its interaction with the insulin-like growth factor 2 binding protein 1 (IGF2BP1), a noncanonical RNA N6-methyladenosine (m6A) modification reader, revealing a novel interplay between RNA modifications and G-quadruplex structures. Knockdown experiments and mutagenesis studies demonstrate that IGF2BP1 binds specifically to the G4 structure, modulating CCN1 mRNA stability. Additionally, we unveil the role of IGF2BP1's RNA recognition motifs in G4 recognition, highlighting this enthalpically driven interaction. Our findings offer fresh perspectives on the complex mechanisms of post-transcriptional gene regulation mediated by G4 RNA secondary structures.

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来源期刊
Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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