Tasic Bosiljka, Nabholz Christoph E, Baldwin Kristin K, Kim Youngwook, Rueckert Erroll H, Ribich Scott A, Cramer Paula, Wu Qiang, Axel Richard, Maniatis Tom
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Mol Cell. 2002 Jul;10(1):21-33. doi: 10.1016/s1097-2765(02)00578-6.
A family of mammalian protocadherin (Pcdh) proteins is encoded by three closely linked gene clusters (alpha, beta, and gamma). Multiple alpha and gamma Pcdh mRNAs are expressed in distinct patterns in the nervous system and are generated by alternative pre-mRNA splicing between different "variable" exons and three "constant" exons within each cluster. We show that each Pcdh variable exon is preceded by a promoter and that promoter choice determines which variable exon is included in a Pcdh mRNA. In addition, we provide evidence that alternative splicing of variable exons within a gene cluster occurs via a cis-splicing mechanism. However, virtually every variable exon can engage in trans-splicing with constant exons from another cluster, albeit at a far lower level.
一个哺乳动物原钙黏蛋白(Pcdh)蛋白家族由三个紧密相连的基因簇(α、β和γ)编码。多个α和γ Pcdh mRNA在神经系统中以不同模式表达,并且是通过每个基因簇内不同“可变”外显子与三个“恒定”外显子之间的可变前体mRNA剪接产生的。我们发现每个Pcdh可变外显子之前都有一个启动子,并且启动子的选择决定了哪个可变外显子被包含在Pcdh mRNA中。此外,我们提供证据表明基因簇内可变外显子的可变剪接是通过顺式剪接机制发生的。然而,实际上每个可变外显子都可以与来自另一个基因簇的恒定外显子进行反式剪接,尽管水平要低得多。