Pre-mRNA splicing in disease and therapeutics. Trends Mol Med 2012 Aug;18(8):472-82
Date
07/24/2012Pubmed ID
22819011Pubmed Central ID
PMC3411911DOI
10.1016/j.molmed.2012.06.006Scopus ID
2-s2.0-84864390703 (requires institutional sign-in at Scopus site) 339 CitationsAbstract
In metazoans, alternative splicing of genes is essential for regulating gene expression and contributing to functional complexity. Computational predictions, comparative genomics, and transcriptome profiling of normal and diseased tissues indicate that an unexpectedly high fraction of diseases are caused by mutations that alter splicing. Mutations in cis elements cause missplicing of genes that alter gene function and contribute to disease pathology. Mutations of core spliceosomal factors are associated with hematolymphoid neoplasias, retinitis pigmentosa, and microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Mutations in the trans regulatory factors that control alternative splicing are associated with autism spectrum disorder, amyotrophic lateral sclerosis (ALS), and various cancers. In addition to discussing the disorders caused by these mutations, this review summarizes therapeutic approaches that have emerged to correct splicing of individual genes or target the splicing machinery.
Author List
Singh RK, Cooper TAMESH terms used to index this publication - Major topics in bold
AnimalsDisease
Genetic Therapy
Humans
Mutation
RNA Precursors
RNA Splicing
Spliceosomes