Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors.
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.
Wang
Junning
J
Shriver Center at UMMS, Waltham, Massachusetts 02452, USA.
Gao
Qing-Sheng
QS
Wang
Yingzi
Y
Lafyatis
Robert
R
Stamm
Stefan
S
Andreadis
Athena
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D003704:Dementia / Q000235:genetics*; D029721:Drosophila Proteins; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012689:Sequence Homology, Nucleic Acid; D016875:tau Proteins / Q000235:genetics*
D029721:Drosophila Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D011506:Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C484205:SFSWAP protein, human; C087691:su(wa) protein, Drosophila; D016875:tau Proteins