Bor Yeou-cherng, Swartz Jennifer, Morrison Avril, Rekosh David, Ladomery Michael, Hammarskjöld Marie-Louise
Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
Genes Dev. 2006 Jun 15;20(12):1597-608. doi: 10.1101/gad.1402306. Epub 2006 May 31.
The Wilms' tumor 1 (WT1) gene plays an important role in mammalian urogenital development, and dysregulation of this gene is observed in many human cancers. Alternative splicing of WT1 RNA leads to the expression of two major protein isoforms, WT1(+KTS) and WT1(-KTS). Whereas WT1(-KTS) acts as a transcriptional regulator, no clear function has been ascribed to WT1(+KTS), despite the fact that this protein is crucial for normal development. Here we show that WT1(+KTS) functions to enhance expression from RNA possessing a retained intron and containing either a cellular or viral constitutive transport element (CTE). WT1(+KTS) expression increases the levels of unspliced RNA containing a CTE and specifically promotes the association of this RNA with polyribosomes. These studies provide further support for links between different steps in RNA metabolism and for the existence of post-transcriptional operons.
肾母细胞瘤1(WT1)基因在哺乳动物泌尿生殖系统发育中起重要作用,并且在许多人类癌症中都观察到该基因的失调。WT1 RNA的可变剪接导致两种主要蛋白质异构体WT1(+KTS)和WT1(-KTS)的表达。尽管WT1(-KTS)作为转录调节因子发挥作用,但尽管WT1(+KTS)对正常发育至关重要,但其尚未被赋予明确的功能。在这里,我们表明WT1(+KTS)的功能是增强具有保留内含子且含有细胞或病毒组成型转运元件(CTE)的RNA的表达。WT1(+KTS)的表达增加了含有CTE的未剪接RNA的水平,并特别促进了这种RNA与多核糖体的结合。这些研究为RNA代谢不同步骤之间的联系以及转录后操纵子的存在提供了进一步的支持。