title: Modulation of the membrane-binding projection domain of tau protein: splicing regulation of exon 3.
abstract: Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. The N-terminal domain of the protein interacts with the axonal membrane, and is modulated by differential inclusion of exons 2 and 3. These two tau exons are alternatively spliced cassettes, in which exon 3 never appears independently of exon 2. Previous work with tau minigene constructs indicated that exon 3 is intrinsically suboptimal and its primary regulator is a weak branch point. In this study, we confirm the role of the weak branch point in the regulation of exon 3 but also show that the exon is additionally regulated by a combination of exonic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 3 isoforms, Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 3.
authors: Department of Biomedical Sciences, E.K. Shriver Center for Mental Retardation, Waltham, MA 02454, USA.
authors: Meltem Cevik
authors: MC
authors: Arikan
authors: John
authors: J
authors: Memmott
authors: Jennifer A
authors: JA
authors: Broderick
authors: Robert
authors: R
authors: Lafyatis
authors: Gavin
authors: G
authors: Screaton
authors: Stefan
authors: S
authors: Stamm
authors: Athena
authors: A
authors: Andreadis
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D022081:Cell Surface Extensions / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins