SPLICING OF A REGULATED EXON REVEALS ADDITIONAL COMPLEXITY IN THE AXONAL MICROTUBULE-ASSOCIATED PROTEIN-TAU

Tau is a microtubule-associated protein whose transcript undergoes com plex regulated splicing in the mammalian nervous system, Exon 6 of the gene is an alternatively spliced cassette whose expression pattern an d splicing regulation had not been previously analyzed in the human. T he expression profile of exon 6 is completely different from that of t he better-analyzed exons 2, 3, 4A, and 10, implying the utilization of distinct regulatory factors. The default splicing behavior of the exo n had demonstrated the existence of what were initially considered cry ptic splice sites. However, analysis of the expression pattern of exon 6 suggests that these splice sites are utilized in certain human tiss ues and, if translated, would result in a radically altered tau protei n. Lastly, expression of exon 6 minigene constructs in cells indicates that its flanking exons are involved in its inclusion and in the modu lation of the ratio of its variants.