FMRP蛋白6种异构体与FXR1蛋白间的相互作用

Interactions between Six FMRP Isoforms and FXR1 ProteinChen YuTing A.Sittler* Yu Min Wu GuanYun JL.Mandel**

脆性Ｘ综合征是最常见的遗传性智力低下疾病，其致病基因ＦＭＲ１存在复杂的选择剪接．ＦＭＲ１基因的功能及其选择剪接的生物学意义尚未阐明．ＦＭＲ１蛋白（ＦＭＲＰ）与脆性Ｘ相关蛋白１（ＦＸＲ１）可形成异源二聚体．采用酵母双杂交体系研究了由ＦＭＲ１第１２、１４、１５外显子不同选择剪接方式产生的６种ＦＭＲＰ异构体与ＦＸＲ１蛋白的相互作用，以期从蛋白质相互作用的角度探讨ＦＭＲ１基因选择剪接表达的生物学意义．结果表明各种异构体与ＦＸＲ１相互作用的强度随异构体蛋白肽链长度的增长而减弱．外显子１２、１４、１５的选择剪接虽然不能开关式控制ＦＭＲＰ与ＦＸＲ１的相互作用，但其Ｃ端亲水区在一定程度上影响相互作用的强弱．提示选择剪接对ＦＭＲＰ与ＦＸＲ１异源二聚体的稳定性产生影响．

Fragile X syndrome is the most common form of hereditary mental retardation,resulting from the lack of expression of fragile x mental retardation gene 1(FMR1).Complex alternative splicing exists during FMR1 expression and leads to various fragile X mental retardation protein(FMRP) isoforms,whose biological roles are not known yet.To find out the effect of alternative splicing on the formation of heterogeneous dimer between FMRP and FXR1,the interactions between six FMRP isoforms resulting from alternative splicing of exons 12,14,15,and FXR1 protein was studied by the use of the yeast twohybrid system.Results show that the strength of interaction decreases as the Cterminus length of the isoforms increases.It suggests that though alternative splicing of exons 12,14,15 has no effect on the interactiveness between FMRP and FXR1,the different Cterminus could effect on the stability of heterogeneous dimer between FMRP and FXR1.