Modulation of the membrane-binding domain of tau protein: splicing regulation of exon 2.
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 regulated 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 2 resembles a constitutive exon. In this study, we show that exon 2 is regulated by a combination of exonic and intronic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 2 isoforms. Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 2.
Li
Karen
K
Division of Neurobiology of Developmental Disorders, Shriver Center for Mental Retardation at UMMS, Waltham, MA 02452, USA.
Arikan
Meltem Cevik
MC
Andreadis
Athena
A
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005091:Exons; D015870:Gene Expression; D000882:Haplorhini; D006801:Humans; D006824:Hybridization, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009447:Neuroblastoma; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D016875:tau Proteins