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Biochim Biophys Acta. 2005 Dec 30;1754(1-2):324-31. Epub 2005 Oct 6.

Alternative splicing: a new drug target of the post-genome era.

Author information

1
Department of Functional Genomics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. m.hagiwara.end@mri.tmd.ac.jp

Abstract

Alternative splicing allows for the creation of multiple distinct mRNA transcripts from a given gene in a multicellular organism. Pre-mRNA splicing is catalyzed by a multi-molecular complex, including serine/arginine-rich (SR) proteins, which are highly phosphorylated in living cells, and thought to play crucial roles in spliceosomal formation and in the regulation of alternative splicing. Recently, reports of low molecular compounds, which alter splicing pattern of genes, have been accumulated. A benzothiazole compound TG003, a kinase inhibitor that targets Clk1 and Clk4, suppressed dissociation of nuclear speckles, altered the splicing patterns, and rescued the embryonic defects induced by excessive Clk activity. The emerging inhibitors of the signal transduction pathways regulating pre-mRNA alternative splicing may open the way to therapies against diseases caused by missplicing.

PMID:
16260193
DOI:
10.1016/j.bbapap.2005.09.010
[Indexed for MEDLINE]
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