Structural study of the disease-related splicing regulatory factors

剪接反应在生物系统的调节中起着重要的作用。要阐明其调控机制，仅凭DNA序列信息是不够的，还需要相关剪接调控因子的结构信息。首先，在本研究中，多剪接因子之间的分子间协调的结构基础进行了研究。本文测定了RBFOX家族蛋白ASD-1和RBM 24-RBM 38家族成员ASD-12的RNA识别基序（RRM）结构域组成的三元复合物的溶液结构，这两个RRM结构域与RNA相互作用形成稳定的复合物。此外，对Tra 2-B剪接因子和靶RNA的研究表明，靶RNA的三级和二级结构影响与相应剪接调节因子的结合特异性。

Splicing reactions plays an important role in the regulation of the biological system. For the elucidation of its regulatory mechanism, the DNA sequence information is not enough and the structural information for the related splicing regulatory factors is necessary. First, in the present study, structural basis for the intermolecular coordination between multi splicing factors is investigated. Here we determined solution structure of a ternary complex composed of the RNA recognition motif (RRM) domains from an RBFOX family protein ASD-1 and a SUP-12-RBM24-RBM38 family member SUP-12 for the alternative splicing of the sole FGFR gene egl-15.The two RRM domains cooperatively interact with the RNA by sandwiching a guanine base to form the stable complex. In addition, investigation of the Tra2-b splicing factor and the target RNA revealed that the ternary and secondary structure of the target RNA affect the binding specificity to the corresponding splicing regulatory factors.