Markus M Andrea, Heinrich Bettina, Raitskin Oleg, Adams David J, Mangs Helena, Goy Christine, Ladomery Michael, Sperling Ruth, Stamm Stefan, Morris Brian J
Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Building F13, The University of Sydney, NSW 2006, Australia.
Exp Cell Res. 2006 Oct 15;312(17):3379-88. doi: 10.1016/j.yexcr.2006.07.008. Epub 2006 Jul 25.
Wilm's tumor protein 1 (WT1), a protein implicated in various cancers and developmental disorders, consists of two major isoforms: WT1(-KTS), a transcription factor, and WT1(+KTS), a post-transcriptional regulator that binds to RNA and can interact with splicing components. Here we show that WT1 interacts with the novel splicing regulator RBM4. Each protein was found to colocalize in nuclear speckles and to cosediment with supraspliceosomes in glycerol gradients. RBM4 conferred dose-dependent and cell-specific regulation of alternative splicing of pre-mRNAs transcribed from several reporter genes. We found that overexpressed WT1(+KTS) abrogated this effect of RBM4 on splice-site selection, whereas WT1(-KTS) did not. We conclude that the (+KTS) form of WT1 is able to inhibit the effect of RBM4 on alternative splicing.
威尔姆斯瘤蛋白1（WT1）是一种与多种癌症和发育障碍相关的蛋白质，它由两种主要的异构体组成：WT1（-KTS），一种转录因子；以及WT1（+KTS），一种与RNA结合并能与剪接成分相互作用的转录后调节因子。在此，我们表明WT1与新型剪接调节因子RBM4相互作用。发现每种蛋白质都共定位于核斑点中，并在甘油梯度中与超剪接体一起沉降。RBM4对几个报告基因转录的前体mRNA的可变剪接具有剂量依赖性和细胞特异性调节作用。我们发现，过表达的WT1（+KTS）消除了RBM4对剪接位点选择的这种影响，而WT1（-KTS）则没有。我们得出结论，WT1的（+KTS）形式能够抑制RBM4对可变剪接的影响。
