## 1 Introduction  
The human [PERSON] tumor gene (WT1), first isolated as a tumor suppressor gene and involved in the development of [PERSON] tumor of the kidney [1], was among the principal tumor suppressor genes to be cloned [2]. The WT1 gene maps to chromosomal band 11p13, and encodes a transcription factor of the zinc finger type family, containing four zinc finger motifs at the _C-terminus_ and a proline/glutamine-rich DNA-binding domain at the _N-terminus_. It spans approximatively 50 kb of genomic sequence and comprises 10 exons that produce a 3 kb mRNA [3, 4]. Numerous isoforms, developing from a combination of alternative translational start sites, alternative RNA splicing, and RNA editing, have been well-documented [5; 6; 7; 8]. The most studied are the exon 5 variants and the KST (lysine-threonine-serine) isoforms, and, in some cases, these can have specific functions. Although WT1 was originally discovered as a tumor suppressor gene involved in the pathogenesis of renal Wilms' tumor, subsequent studies emphasized its potential oncogenic role in hematologic malignancies [9] and in different malignant solid tumors [10], including lung cancer [11], colorectal cancer [12], pancreatic cancer [13], breast cancer [14], desmoid tumors [15], ovarian cancer [16; 17], brain tumors [18; 19] and soft tissue sarcomas [20]. This hypothesis is supported by several functional studies showing that WT1 inhibition, by using antisense oligonucleotides, reduces cell proliferation, migration and endothelial tube formation [21]. WT1 could play an important role in angiogenesis, the onset of metastases and the inhibition of the immune response. In fact the endothelial cells, haematopoietic progenitor and myeloid-derived suppressor cells express high levels of WT1 inducing the control of the expression of CD31 and CD117. Therefore, the inactivation of WT1 in the aforementioned cells can reduce angiogenesis, the development of metastases and promote the immune response [22]. Although the first function defined for WT1 was that of a transcriptional regulator, in the last 10 years several studies have emerged indicating its function as an activator, a repressor or a coactivator [23; 24]. Nevertheless, it is known that the role of WT1 is more complicated than once believed, and it could be involved in at least two distinct cellular processes: transcription control and RNA metabolism. All these roles of WT1 are supported by alternative splicing of the WT1 RNA to generate two main isoforms that differ by the insertion of three amino acids, KTS (lysine-threonine-serine), inside the zinc finger region of the protein [25; 26; 27]. In this regard, several studies have demonstrated that the isoform of WT1 that lacks the KTS insertion, -KTS WT1, binds to DNA with higher affinity and functions as a transcriptional regulator. On the other hand, the form having the KTS insertion, +KTS WT1, plays a role in mRNA splicing rather than transcriptional control [28; 29]. [PERSON] et al. found the first correlation between the WT1 protein and RNA metabolism, showing that the +KTS WT1 isoform colocalized specially with splicing factors within nuclear speckles. In the last few years it has been demonstrated that a considerable amount of transcription and/or splicing factors shuttle to the cytoplasm, acquiring a new function. The cytoplasmic role attributed to shuttling proteins is predominantly the nucleocytoplasmic transport of mRNA or RNA. [PERSON] et al. [27], emphasized not only that WT1 is a shuttling protein, but also that a substantial part of endogenous WT1 protein is located in the cytoplasm. Furthermore, they showed that both WT1 isoforms shuttle between the nucleus and the cytoplasm [30]. WT1 is not only differentially spliced, but in turn alters the splicing and function of other genes, such as the vascular endothelial growth factor (VEGF), through the activation of Serine/arginine-rich, protein-specific splicing factor kinase (SRPK1), and indirectly Serine/arginine-rich splicing factor 1 (Srsf1).