Journal
JOURNAL OF NEUROCHEMISTRY
Volume 88, Issue 5, Pages 1078-1090Publisher
WILEY
DOI: 10.1046/j.1471-4159.2003.02232.x
Keywords
alternative splicing; cis regulatory element and trans splicing regulator; frontotemporal dementia; MAP tau; regulated isoform
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Funding
- NIA NIH HHS [AG18486] Funding Source: Medline
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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.
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