Boehringer Ashley, Bowser Robert
Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA.
School of Life Sciences, Arizona State University, Phoenix, AZ, USA.
Adv Neurobiol. 2018;20:85-101. doi: 10.1007/978-3-319-89689-2_4.
In eukaryotic cells, transcription and translation are compartmentalized by the nuclear membrane, requiring an active transport of RNA from the nucleus into the cytoplasm. This is accomplished by a variety of transport complexes that contain either a member of the exportin family of proteins and translocation fueled by GTP hydrolysis or in the case of mRNA by complexes containing the export protein NXF1. Recent evidence indicates that RNA transport is altered in a number of different neurodegenerative diseases including Huntington's disease, Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Alterations in RNA transport predominately fall into three categories: Alterations in the nuclear membrane and mislocalization and aggregation of the nucleoporins that make up the nuclear pore; alterations in the Ran gradient and the proteins that control it which impacts exportin based nuclear export; and alterations of proteins that are required for the export of mRNA leading nuclear accumulation of mRNA.
在真核细胞中，转录和翻译被核膜分隔开，这就需要RNA从细胞核主动运输到细胞质中。这是通过多种转运复合物来完成的，这些复合物要么包含输出蛋白家族的一种蛋白质成员，并由GTP水解提供动力进行转运，要么对于mRNA而言，是由包含输出蛋白NXF1的复合物来完成转运。最近的证据表明，在许多不同的神经退行性疾病中，包括亨廷顿舞蹈症、阿尔茨海默病、额颞叶痴呆和肌萎缩侧索硬化症，RNA运输都会发生改变。RNA运输的改变主要分为三类：核膜的改变以及构成核孔的核孔蛋白的错误定位和聚集；Ran梯度以及控制它的蛋白质的改变，这会影响基于输出蛋白的核输出；以及mRNA输出所需蛋白质的改变，导致mRNA在细胞核中积累。
