Division of Cosmetic Science and Technology, Daegu Haany University, Hanuidae-ro 1, Gyeongsan, Gyeongbuk 38610, Korea.
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
Int J Mol Sci. 2021 Mar 5;22(5):2598. doi: 10.3390/ijms22052598.
Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of the disease-causing RNA or proteins encoded by these genes form aggregates and disrupt cellular function related to RNA metabolism. Disease-related RNA or proteins interact or sequester other RNA-binding proteins. Eventually, many disease-causing mutations lead to the dysregulation of nucleocytoplasmic shuttling, the dysfunction of stress granules, and the altered dynamic function of the nucleolus as well as other membrane-less organelles. As RNA-binding proteins are usually components of several RNA-binding protein complexes that have other roles, the dysregulation of RNA-binding proteins tends to cause diverse forms of cellular dysfunction. Therefore, understanding the role of RNA-binding proteins will help elucidate the complex pathophysiology of ALS. Here, we summarize the current knowledge regarding the function of disease-associated RNA-binding proteins and their role in the dysfunction of membrane-less organelles.
对肌萎缩侧索硬化症（ALS）患者的遗传分析已经确定了致病突变，并加速了复杂的分子发病机制的揭示，这对于理解疾病和开发治疗策略可能很重要。许多与疾病相关的基因编码 RNA 结合蛋白，并且这些基因编码的大多数致病 RNA 或蛋白质形成聚集体并破坏与 RNA 代谢相关的细胞功能。与疾病相关的 RNA 或蛋白质相互作用或隔离其他 RNA 结合蛋白。最终，许多致病突变导致核质穿梭的失调、应激颗粒的功能障碍以及核仁以及其他无膜细胞器的动态功能的改变。由于 RNA 结合蛋白通常是具有其他作用的几个 RNA 结合蛋白复合物的组成部分，因此 RNA 结合蛋白的失调往往会导致多种形式的细胞功能障碍。因此，了解 RNA 结合蛋白的作用将有助于阐明 ALS 的复杂病理生理学。在这里，我们总结了与疾病相关的 RNA 结合蛋白的功能及其在无膜细胞器功能障碍中的作用的最新知识。
