Department of Developmental and Molecular Biology and Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York.
Department of Developmental and Molecular Biology, Department of Medicine (Oncology), and Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York.
Wiley Interdiscip Rev RNA. 2019 Jul;10(4):e1532. doi: 10.1002/wrna.1532. Epub 2019 Mar 20.
Splicing is the global cellular process whereby intervening sequences (introns) in precursor messenger RNA (pre-mRNA) are removed and expressed regions (exons) are ligated together, resulting in a mature mRNA transcript that is exported and translated in the cytoplasm. The tightly regulated splicing cycle is also flexible allowing for the inclusion or exclusion of some sequences depending on the specific cellular context. Alternative splicing allows for the generation of many transcripts from a single gene, thereby expanding the proteome. Although all cells require the function of the spliceosome, neurons are highly sensitive to splicing perturbations with numerous neurological diseases linked to splicing defects. The sensitivity of neurons to splicing alterations is largely due to the complex neuronal cell types and functions in the nervous system that require specific splice isoforms to maintain cellular homeostasis. In the past several years, the relationship between RNA splicing and the nervous system has been the source of significant investigation. Here, we review the current knowledge on RNA splicing in neurobiology and discuss its potential role and impact in neurodegenerative diseases. We will examine the impact of alternative splicing and the role of splicing regulatory proteins on neurodegeneration, highlighting novel animal models including mouse and zebrafish. We will also examine emerging technologies and therapeutic interventions that aim to "drug" the spliceosome. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Development.
剪接是一种普遍的细胞过程，通过该过程，前体信使 RNA（pre-mRNA）中的间隔序列（内含子）被去除，表达区域（外显子）被连接在一起，产生成熟的 mRNA 转录本，该转录本被输出并在细胞质中翻译。剪接周期受到严格调控，但也具有灵活性，允许根据特定的细胞环境包含或排除一些序列。选择性剪接允许从单个基因产生许多转录本，从而扩大蛋白质组。尽管所有细胞都需要剪接体的功能，但神经元对剪接扰动非常敏感，许多神经疾病都与剪接缺陷有关。神经元对剪接改变的敏感性在很大程度上是由于神经系统中复杂的神经元细胞类型和功能需要特定的剪接异构体来维持细胞内稳态。在过去的几年中，RNA 剪接与神经系统之间的关系一直是大量研究的来源。在这里，我们回顾了神经生物学中 RNA 剪接的现有知识，并讨论了它在神经退行性疾病中的潜在作用和影响。我们将研究选择性剪接的影响和剪接调节蛋白在神经退行性变中的作用，重点介绍包括小鼠和斑马鱼在内的新型动物模型。我们还将研究旨在“药物”剪接体的新兴技术和治疗干预措施。本文属于以下类别：RNA 在疾病与发展 > RNA 在疾病中的作用 RNA 加工 > 剪接调控/选择性剪接 RNA 在疾病与发展 > RNA 在发展中的作用。
