Modulation of DNA Binding Specificity by Alternative Splicing of the Wilms Tumor wt1 Gene Transcript

• Published in: Science (American Association for the Advancement of Science) 1992-07, Vol.257 (5067), p.235-237
• Main Authors: Bickmore, W. A., Oghene, K., Little, M. H., Seawright, A., van Heyningen, V., Hastie, N. D.
• Format: Article
• Language: English
• Subjects: Alternative splicing; Amino Acid Sequence; Amino acids; Base Sequence; binding; Binding sites; Binding Sites - genetics; Binding, Competitive; Biological and medical sciences; Chromosomes, Human, Pair 11; DNA; DNA - metabolism; DNA binding proteins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fingers; Fundamental and applied biological sciences. Psychology; Genes; Genetic aspects; Genomics; Humans; man; modulation; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nephroblastoma; Oligonucleotides; Polymerase Chain Reaction; RNA Splicing; RNA, Messenger - metabolism; Sequence Homology, Nucleic Acid; specificity; splicing; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Wilms Tumor - genetics; Wilms' tumor; wt1 gene; WT1 Proteins; Zinc; Zinc Fingers - genetics
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1321494

The technique of whole-genome polymerase chain reaction was used to study the DNA binding properties of the product of the wt1 gene. The zinc finger region of this gene is alternatively spliced such that the major transcript encodes a protein with three extra amino acids between the third and fourth fingers. The minor form of the protein binds specifically to DNA. It is now shown that the major form of wt1 messenger RNA encodes a protein that binds to DNA with a specificity that differs from that of the minor form. Therefore, alternative splicing within the DNA binding domain of a transcription factor can generate proteins with distinct DNA binding specificities and probably different physiological targets.