Alternative splicing: A new drug target of the post-genome era
Alternative splicing: A new drug target of the post-genome era
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DOI：
10.1016/j.bbapap.2005.09.010
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发表时间：
2005-12-30
影响因子：
3.2
通讯作者：
Hagiwara, M
中科院分区：
文献类型：
--
作者：
Hagiwara, M
选择性剪接允许在多细胞生物体中从给定基因产生多个不同的mRNA转录物。前体mRNA剪接由多分子复合物催化，包括富含丝氨酸/丝氨酸（SR）的蛋白，其在活细胞中高度磷酸化，并且被认为在剪接体形成和选择性剪接的调节中起关键作用。近年来，关于改变基因剪接模式的小分子化合物的报道越来越多。一种苯并噻唑化合物TG 003，一种靶向Clk 1和Clk 4的激酶抑制剂，抑制了核斑点的解离，改变了剪接模式，并挽救了由过度Clk活性诱导的胚胎缺陷。新出现的调节前体mRNA选择性剪接的信号转导通路抑制剂可能为治疗由错误剪接引起的疾病开辟了道路。(c)2005 Elsevier B.V保留所有权利。
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 CIk4, 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. (c) 2005 Elsevier B.V All rights reserved.