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The Wilms tumour suppressor protein WT1 (+KTS isoform) binds alpha-actinin 1 mRNA via its zinc-finger domain

Morrison, A. A.; Venables, J. P.; Dellaire, G.; Ladomery, Michael

Authors

A. A. Morrison

J. P. Venables

G. Dellaire



Abstract

Mutations in WT1 are associated with developmental syndromes that affect the urogenital system and neoplasms, including Wilms tumour, acute myeloid leukemia, and breast and prostate cancers. The WT1 protein belongs to the early growth response family of zinc-finger transcription factors. Uniquely to WT1, an evolutionarily conserved alternative splice event inserts the tripeptide KTS, between zinc fingers 3 and 4. Whereas -KTS isoforms bind DNA and activate or repress transcription, +KTS isoforms bind DNA less efficiently and interact with splice factors and RNA in vitro and in vivo. Although candidate DNA targets have been found, physiological mRNA targets are yet to be defined. We examined the distribution of WT1 in ribonucleoprotein (RNP) complexes in nuclear extract prepared from M15 cells, a mouse mesonephric fetal kidney cell line. WT1 cofractionated with the splice factor PSF in large RNP particles ≥2 MDa. We also found that PSF co-immunoprecipitated with WT1, suggesting a functional interaction between these 2 multifunctional proteins. Using yeast three-hybrid library constructed from the co-immunoprecipitated RNA we found that WT1 (+KTS) binds close to or at the start codon of alpha-actinin 1 (ACTN1) mRNA. A band shift assay confirmed the ability of the WT1 zinc-finger domain (+KTS) to bind this sequence in vitro. ACTN1 is the first likely physiological mRNA target of WT1. © 2006 NRC Canada.

Citation

Morrison, A. A., Venables, J. P., Dellaire, G., & Ladomery, M. (2006). The Wilms tumour suppressor protein WT1 (+KTS isoform) binds alpha-actinin 1 mRNA via its zinc-finger domain. Biochemistry and Cell Biology, 84(5), 789-798. https://doi.org/10.1139/O06-065

Journal Article Type Article
Publication Date Oct 1, 2006
Journal Biochemistry and Cell Biology
Print ISSN 0829-8211
Publisher Canadian Science Publishing
Peer Reviewed Peer Reviewed
Volume 84
Issue 5
Pages 789-798
DOI https://doi.org/10.1139/O06-065
Keywords WT1, PSF, alpha-actinin, yeast three-hybrid screen
Public URL https://uwe-repository.worktribe.com/output/1041777
Publisher URL http://dx.doi.org/10.1139/O06-065