Aberrant RNA processing events in neurological disorders.

The importance of aberrant RNA processing in neurodegeneration is becoming increasingly clear; a recent example being the identification of the splicing factor TDP-43 as the major component of inclusions characteristic of a number of neurodegenerative conditions including amyotrophic lateral sclerosis (ALS). Due to the enormous diversity generated by alternative splicing and its importance in the nervous system, it is no surprise that defective alternative splicing in disease has been particularly well documented. However, in addition to splicing, other RNA processing events such as RNA editing, polyadenylation and mRNA stability are also disrupted in some neurological disorders. For instance: the editing efficiency of specific ionotropic receptors is reduced in ALS affecting ion permeability and the function of RNA-processing proteins is affected by their sequestration to trinucleotide repeat expanded mRNAs in several disorders. Due to the extensive coupling between RNA processing events and the multifunctionality of the RNA processing factors that regulate them, it is important to consider RNA processing as a whole. Here we review RNA processing events and their extensive coupling to one another and detail the associations of RNA processing including, but not exclusively, alternative splicing with neurodegeneration. Copyright (c) 2010 Elsevier B.V. All rights reserved.