WT1以一种异构体依赖的方式与剪接因子U2AF65相互作用，并可被整合到剪接体中。
WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes.
作者信息
Davies R C, Calvio C, Bratt E, Larsson S H, Lamond A I, Hastie N D
机构信息
Medical Research Council (MRC) Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
出版信息
Genes Dev. 1998 Oct 15;12(20):3217-25. doi: 10.1101/gad.12.20.3217.
Abstract
WT1 is essential for normal kidney development, and genetic alterations are associated with Wilms' tumor, Denys Drash (DDS), and Frasier syndromes. Although generally considered a transcription factor this study has revealed that WT1 interacts with an essential splicing factor, U2AF65, and associates with the splicing machinery. WT1 is alternatively spliced and isoforms that include three amino acids, KTS, show stronger interaction with U2AF65 in vitro and better colocalization with splicing factors in vivo. Interestingly a mutation associated with DDS enhanced both -KTS WT1 binding to U2AF65 and splicing-factor colocalization. These data illustrate the functional importance of WT1 isoforms and suggest that WT1 plays a role in pre-mRNA splicing.
摘要
WT1对于正常肾脏发育至关重要，基因改变与威尔姆斯瘤、迪尼-德拉斯（DDS）综合征和弗雷泽综合征相关。尽管通常被认为是一种转录因子，但本研究表明WT1与一种关键的剪接因子U2AF65相互作用，并与剪接机制相关联。WT1存在可变剪接，包含三个氨基酸KTS的异构体在体外与U2AF65的相互作用更强，在体内与剪接因子的共定位更好。有趣的是，与DDS相关的一种突变增强了-KTS WT1与U2AF65的结合以及与剪接因子的共定位。这些数据说明了WT1异构体的功能重要性，并表明WT1在mRNA前体剪接中发挥作用。
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