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Trends Mol Med. 2012 Aug;18(8):472-82. doi: 10.1016/j.molmed.2012.06.006. Epub 2012 Jul 18.

Pre-mRNA splicing in disease and therapeutics.

Author information

1
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

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.

PMID:
22819011
PMCID:
PMC3411911
DOI:
10.1016/j.molmed.2012.06.006
[Indexed for MEDLINE]
Free PMC Article

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