The Wilms’ tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron

Abstract

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.

Real-time PCR quantification of major Wilms’ tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences

“…15,34 Functional studies suggest that many of WT1 effects are related to particular WT1 isoforms. 8,20,[35][36][37][38][39][40] The available data on WT1 isoform expression patterns in normal and malignant hematopoiesis are scarce and the methods so far used for the detection of WT1 major isoforms (reverse transcriptase PCR, GeneScan, quantitative PCR of EX5[ þ ] and KTS[ þ ] variants) have only yielded an approximate estimation of WT1 isoform levels.…”

Transcriptional Regulation by the Wilms Tumor Protein, Wt1, Suggests a Role of the Metalloproteinase Adamts16 in Murine Genitourinary Development

“…Structural and functional data demonstrate that Wt1(ϪKTS) proteins, which lack the 3 amino acids, act as transcription factors (37,38). Compared with the Wt1(ϪKTS) isoforms, Wt1 proteins with the KTS insertion exhibit increased RNA binding affinity and play a presumed role in mRNA processing (39,40). The human osteosarcomaderived cell lines UB27 and UD28 express the Wt1(ϪKTS) and Wt1(ϩKTS) proteins, respectively, under control of a tetracycline-dependent promoter (23).…”

Transcriptional Regulation of the Human Thromboxane A2 Receptor Gene by Wilms’ Tumour (WT)

“…In addition to acting as a regulator of transcription, WT1 can also play a role in post-transcriptional regulation, including in RNA splicing (74,75), and also in translation (76). Such diverse functions are likely due to fact that WT1 protein exists as multiple isoforms that arise owing to differential splicing and/or the use of multiple translational initiation sites within the WT1 gene (77).…”