Lallena María José, Chalmers Kevin J, Llamazares Salud, Lamond Angus I, Valcárcel Juan
Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.
Cell. 2002 May 3;109(3):285-96. doi: 10.1016/s0092-8674(02)00730-4.
The Drosophila protein Sex-lethal (SXL) promotes skipping of exon 3 from its own pre-mRNA. An unusual sequence arrangement of two AG dinucleotides and an intervening polypyrimidine (Py)-tract at the 3' end of intron 2 is important for Sxl autoregulation. Here we show that U2AF interacts with the Py-tract and downstream AG, whereas the spliceosomal protein SPF45 interacts with the upstream AG and activates it for the second catalytic step of the splicing reaction. SPF45 represents a new class of second step factors, and its interaction with SXL blocks splicing at the second step. These results are in contrast with other known mechanisms of splicing regulation, which target early events of spliceosome assembly. A similar role for SPF45 is demonstrated in the activation of a cryptic 3' ss generated by a mutation that causes human beta-thalassemia.
果蝇的性致死蛋白（SXL）可促使其自身前体mRNA的外显子3跳跃。内含子2 3'端两个AG二核苷酸和一个居间的多嘧啶（Py）序列的异常排列对Sxl的自我调节很重要。我们在此表明，U2AF与Py序列及下游AG相互作用，而剪接体蛋白SPF45与上游AG相互作用，并在剪接反应的第二步激活该上游AG。SPF45代表一类新的第二步因子，它与SXL的相互作用会在第二步阻断剪接。这些结果与其他已知的剪接调控机制形成对比，后者针对剪接体组装的早期事件。在由导致人类β地中海贫血的突变产生的隐蔽3'剪接位点的激活过程中，也证明了SPF45具有类似作用。
