Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Wiley Interdiscip Rev RNA. 2024 Mar-Apr;15(2):e1838. doi: 10.1002/wrna.1838.
Disruptions in spatiotemporal gene expression can result in atypical brain function. Specifically, autism spectrum disorder (ASD) is characterized by abnormalities in pre-mRNA splicing. Abnormal splicing patterns have been identified in the brains of individuals with ASD, and mutations in splicing factors have been found to contribute to neurodevelopmental delays associated with ASD. Here we review studies that shed light on the importance of splicing observed in ASD and that explored the intricate relationship between splicing factors and ASD, revealing how disruptions in pre-mRNA splicing may underlie ASD pathogenesis. We provide an overview of the research regarding all splicing factors associated with ASD and place a special emphasis on five specific splicing factors-HNRNPH2, NOVA2, WBP4, SRRM2, and RBFOX1-known to impact the splicing of ASD-related genes. In the discussion of the molecular mechanisms influenced by these splicing factors, we lay the groundwork for a deeper understanding of ASD's complex etiology. Finally, we discuss the potential benefit of unraveling the connection between splicing and ASD for the development of more precise diagnostic tools and targeted therapeutic interventions. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Evolution and Genomics > Computational Analyses of RNA RNA-Based Catalysis > RNA Catalysis in Splicing and Translation.
时空基因表达的紊乱可能导致异常的大脑功能。具体来说，自闭症谱系障碍（ASD）的特征是前体 mRNA 剪接异常。在 ASD 患者的大脑中已经发现了异常的剪接模式，并且已经发现剪接因子的突变导致与 ASD 相关的神经发育迟缓。在这里，我们回顾了一些阐明 ASD 中观察到的剪接重要性的研究，并探讨了剪接因子与 ASD 之间的复杂关系，揭示了前体 mRNA 剪接的紊乱如何成为 ASD 发病机制的基础。我们概述了与 ASD 相关的所有剪接因子的研究，并特别强调了五个特定的剪接因子——HNRNPH2、NOVA2、WBP4、SRRM2 和 RBFOX1——它们已知会影响 ASD 相关基因的剪接。在讨论这些剪接因子影响的分子机制时，我们为更深入地了解 ASD 复杂的病因学奠定了基础。最后，我们讨论了揭示剪接与 ASD 之间联系的潜在好处，以便为开发更精确的诊断工具和靶向治疗干预措施提供依据。本文属于以下分类：疾病和发育中的 RNA > RNA 在疾病中的作用 RNA 的进化和基因组学 > RNA 和核糖核蛋白的进化 RNA 的进化和基因组学 > 对 RNA 的计算分析 > RNA 在剪接和翻译中的催化作用。
