Tau exon 6 is regulated by an intricate interplay of trans factors and cis elements, including multiple branch points.
Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 6 of the gene is an alternatively spliced cassette whose expression profile differs from that of the other tau regulated exons, implying the involvement of distinct regulatory factors. Previous work had established the existence and use of two additional 3' splice sites within exon 6 and the influence of splicing factors polypyrimidine binding protein (PTB) and U2AF on its splicing. The present work shows that exon 6 isoforms exist in distinct ratios in different compartments of the nervous system and that splicing of exon 6 is governed by multiple branch points, exonic cis elements and additional trans factors. Recent results show that tau exon 6 is specifically suppressed in the brains of people who suffer from myotonic dystrophy type 1. The understanding of how tau exon 6 splicing is regulated may give us insights into the disease.
Wang
Junning
J
Shriver Center at University of Massachusetts Medical School, Waltham, Massachusetts 02452, USA.
Tse
Sze-Wah
SW
Andreadis
Athena
A
D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005091:Exons / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000502:physiology; D016875:tau Proteins / Q000235:genetics*
D022821:RNA Splice Sites; D012333:RNA, Messenger; D015534:Trans-Activators; D016875:tau Proteins