PUBLICATION
Alternative splicing of Wilms tumor suppressor 1 (Wt1) exon 4 results in protein isoforms with different functions
- Authors
- Schnerwitzki, D., Perner, B., Hoppe, B., Pietsch, S., Mehringer, R., Hänel, F., Englert, C.
- ID
- ZDB-PUB-140712-2
- Date
- 2014
- Source
- Developmental Biology 393(1): 24-32 (Journal)
- Registered Authors
- Englert, Christoph, Perner, Birgit
- Keywords
- Glomerulus, Kidney development, Morpholino, Pronephros, Transcription factor, Zebrafish
- MeSH Terms
-
- Alternative Splicing/genetics*
- Amino Acid Sequence
- Animals
- Base Sequence
- Cloning, Molecular
- Cyprinodontiformes/embryology
- Cyprinodontiformes/genetics
- Fishes/abnormalities*
- Fishes/genetics
- Fundulidae/embryology
- Fundulidae/genetics
- Gene Expression Regulation, Developmental
- Gene Knockout Techniques
- Kidney/abnormalities*
- Molecular Sequence Data
- Morpholinos/genetics
- Oryzias/embryology
- Oryzias/genetics
- Poecilia/embryology
- Poecilia/genetics
- Pronephros/abnormalities*
- Protein Isoforms/genetics
- Protein Multimerization
- Sequence Alignment
- Sequence Analysis, DNA
- Two-Hybrid System Techniques
- WT1 Proteins/genetics*
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 25014653 Full text @ Dev. Biol.
Citation
Schnerwitzki, D., Perner, B., Hoppe, B., Pietsch, S., Mehringer, R., Hänel, F., Englert, C. (2014) Alternative splicing of Wilms tumor suppressor 1 (Wt1) exon 4 results in protein isoforms with different functions. Developmental Biology. 393(1):24-32.
Abstract
The Wilms tumor suppressor gene Wt1 encodes a zinc finger transcription factor that is essential for development of multiple organs including kidneys, gonads, spleen and heart. In mammals Wt1 comprises 10 exons with two characteristic splicing events: inclusion or skipping of exon 5 and alternative usage of two splice donor sites between exons 9 and 10. Most fish including zebrafish and medaka possess two wt1 paralogs, wt1a and wt1b, both lacking exon 5. Here we have characterized wt1 in guppy, platyfish and the short-lived African killifish Nothobranchius furzeri. All fish except zebrafish show alternative splicing of exon 4 of wt1a but not of wt1b with the wt1a(-exon 4) isoform being the predominant splice variant. With regard to function, Wt1a(+exon 4) showed less dimerization but stimulated transcription more effectively than the Wt1a(-exon 4) isoform. A specific knockdown of wt1a exon 4 in zebrafish was associated with anomalies in kidney development demonstrating a physiological function for Wt1a exon 4. Interestingly, alternative splicing of exon 4 seems to be an early evolutionary event as it is observed in the single wt1 gene of the sturgeon, a species that has not gone through teleost-specific genome duplication.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping