RNA Nucleocytoplasmic Transport Defects in Neurodegenerative Diseases

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.