Differential splicing of exon 5 of the Wilms tumour (WTI) gene.
The WTI gene encodes a developmentally regulated transcription factor whose function is altered by alternative splicing at two sites: the 17 amino acids of exon 5, whose functional effects are ill-defined, and the 3 amino acids (KTS) between exons 9 and 10, which determine sequence-specific DNA binding and nuclear localisation. Germline mutations, which prevent normal KTS splicing, can underlie the Denys-Drash syndrome, and disruptions of splicing of exon 5 may occur in Wilms tumours. We analysed by reverse transcriptase polymerase chain reaction (RT-PCR) amplification the relative ratios of the four splice variants of WTI mRNA in normal and tumour tissues and found tissue-specific, developmental stage-specific, and species-specific differences in the splicing of exon 5 but not of KTS. We found no evidence for disrupted splicing in acute leukaemias or gonadal tumours. The significance of these findings is discussed, and the possibility is raised that WTI may orchestrate the appropriate response to growth and differentiation factor signalling, mediated by alterations in the relative levels of exon 5 containing WTI isoforms.
Renshaw
J
J
Section of Paediatrics, Institute of Cancer Research, Surrey, United Kingdom.
King-Underwood
L
L
Pritchard-Jones
K
K
D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016162:Genes, Wilms Tumor / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D008221:Lymphoid Tissue / Q000737:chemistry / Q000166:cytology; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000302:isolation & purification; D012194:RNA-Directed DNA Polymerase; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured; D014565:Urogenital Neoplasms / Q000235:genetics / Q000473:pathology
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012194:RNA-Directed DNA Polymerase