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Published on: February 22, 2014
Characterization of multiple transcripts and isoforms derived from the mouse protein tyrosine phosphatase gene Ptprr
Renato G S Chirivi1, Gönül Dilaver, Rinske van de Vorstenbosch
1Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, University of Nijmegen, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
Abstract:
The use of alternative splice sites, promoters and translation start sites considerably adds to the complexity of organisms. Four mouse cDNAs (PTPBR7, PTP-SL, PTPPBSgamma+ and PTPPBSgamma-) have been cloned that contain different 5' parts but encode identical protein tyrosine phosphatase PTPRR catalytic domains. We investigated the genomic origin and coding potential of these transcripts to elucidate their interrelationship. Mouse gene Ptprr exons were identified within a 260 kbp segment on chromosome 10, revealing PTP-SL- and PTPPBSgamma-specific transcription start sites within introns two and four, respectively, relative to the 14 PTPBR7 exons. Northern and RT-PCR analyses demonstrated differential expression patterns for these promoters. Furthermore, transfection studies and AUG codon mutagenesis demonstrated that in PTP-SL and PTPPBSgamma messengers multiple translation initiation sites are being used. Resulting 72, 60, 42 and 37 kDa PTPRR protein isoforms differ not only in the length of their N-terminal part but also in their subcellular localization, covering all major PTP subtypes; receptor-like, membrane associated and cytosolic. In summary, mouse gene Ptprr gives rise to multiple isoforms through the use of distinct promoters, alternative splicing and differential translation starts. These results set the stage for further investigations on the physiological roles of PTPRR proteins.
Insights
The mouse Ptprr gene generates diverse protein tyrosine phosphatase PTPRR isoforms. This complexity arises from alternative promoters, splicing, and translation start sites, influencing protein function and localization.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Organismal complexity increases with alternative splicing, promoters, and translation start sites.
- Four mouse cDNAs (PTPBR7, PTP-SL, PTPPBSgamma+, PTPPBSgamma-) encode identical protein tyrosine phosphatase PTPRR catalytic domains but differ in 5' regions.
Purpose of the Study:
- Investigate the genomic origin and coding potential of mouse PTPRR transcripts.
- Elucidate the interrelationship between different PTPRR cDNA variants.
Main Methods:
- Gene mapping of mouse Ptprr on chromosome 10.
- Northern and RT-PCR analyses for differential gene expression.
- Transfection studies and AUG codon mutagenesis to identify translation initiation sites.
Main Results:
- Ptprr exons span 260 kbp on chromosome 10.
- PTP-SL and PTPPBSgamma-specific transcription start sites identified within introns.
- Differential expression patterns observed for distinct promoters.
- Multiple translation initiation sites utilized in PTP-SL and PTPPBSgamma transcripts.
- Resulting PTPRR protein isoforms (72, 60, 42, 37 kDa) exhibit varied N-terminal lengths and subcellular localizations (receptor-like, membrane-associated, cytosolic).
Conclusions:
- Mouse Ptprr gene produces multiple protein isoforms via distinct promoters, alternative splicing, and differential translation initiation.
- These findings provide a foundation for exploring the physiological roles of PTPRR proteins.

