Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors

被引:80
作者
Wang, JN
Gao, QS
Wang, YZ
Lafyatis, R
Stamm, S
Andreadis, A
机构
[1] UMMS, Shriver Ctr, Waltham, MA 02452 USA
[2] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA
[3] Boston Univ, Sch Med, Ctr Arthritis, Boston, MA 02118 USA
[4] Univ Erlangen Nurnberg, Erlangen, Germany
关键词
alternative splicing; cis regulatory element and trans splicing regulator; frontotemporal dementia; MAP tau; regulated isoform;
D O I
10.1046/j.1471-4159.2003.02232.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. In humans, exon 10 of the gene is an alternatively spliced cassette which is adult-specific and which codes for a microtubule binding domain. Mutations that affect splicing of exon 10 have been shown to cause inherited frontotemporal dementia (FTDP). In this study, we reconstituted naturally occurring exon 10 FTDP mutants and classified their effects on its splicing. We also carried out a comprehensive survey of the influence of splicing regulators on exon 10 inclusion and tentatively identified the site of action for several of these factors. Lastly, we identified the domains of regulators SWAP and hnRNPG, which are required for regulation of exon 10 splicing.
引用
收藏
页码:1078 / 1090
页数:13
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