PURPOSE: Alternative RNA splicing is essential in development and more rapid physiological processes that include disease mechanisms. Studies over the last 20 years demonstrated that RNA binding protein families, which mediate the alternative splicing of a large percentage of genes in mammals, contain isoforms with mutually exclusive expression in non-neural and neural progenitor cells vs. post-mitotic neurons, and regulate the comprehensive reprogramming of alternative splicing during neurogenesis. Polypyrimidine tract binding (PTB) proteins and Fox-1 proteins also undergo mutually exclusive alternative splicing in neural and non-neural cells that regulates their tissue-specific expression and splicing activities. Over the past 50 years, striking morphological similarities noted between lens fiber cells and neurons suggested that cell biology processes and gene expression profiles may be shared as well. Here, we examined mouse and rat lenses to determine if alternative splicing of neuronal nPTB and Fox-1/Fox-2 isoforms also occurs in lenses. METHODS: Immunoblot, immunofluorescence, and RT-PCR were used to examine expression and alternative splicing of transcripts in lens and brain. RESULTS: We demonstrated that exon 10 is predominantly included in nPTB transcripts consistent with nPTB protein in lenses, and that alternatively spliced Fox-1/-2 lens transcripts contain exons that have been considered neuron-specific. We identified a 3' alternative Fox-1 exon in lenses that encodes a nuclear localization signal consistent with its protein distribution detected in fiber cells. Neuronal alternative splicing of kinesin KIF1Bβ2 has been associated with PTB/nPTB and Fox-2, and we found that two 'neuron-specific' exons are also included in lenses. CONCLUSIONS: The present study provides evidence that alternative neuronal nPTB and Fox-1/Fox-2 isoforms are also produced in lenses. These findings raise questions regarding the extent these factors contribute to a similar reprogramming of alternative splicing during lens differentiation, and the degree that alternative gene transcripts produced during neurogenesis are also expressed in the lens.
PURPOSE: Alternative RNA splicing is essential in development and more rapid physiological processes that include disease mechanisms. Studies over the last 20 years demonstrated that RNA binding protein families, which mediate the alternative splicing of a large percentage of genes in mammals, contain isoforms with mutually exclusive expression in non-neural and neural progenitor cells vs. post-mitotic neurons, and regulate the comprehensive reprogramming of alternative splicing during neurogenesis. Polypyrimidine tract binding (PTB) proteins and Fox-1 proteins also undergo mutually exclusive alternative splicing in neural and non-neural cells that regulates their tissue-specific expression and splicing activities. Over the past 50 years, striking morphological similarities noted between lens fiber cells and neurons suggested that cell biology processes and gene expression profiles may be shared as well. Here, we examined mouse and rat lenses to determine if alternative splicing of neuronal nPTB and Fox-1/Fox-2 isoforms also occurs in lenses. METHODS: Immunoblot, immunofluorescence, and RT-PCR were used to examine expression and alternative splicing of transcripts in lens and brain. RESULTS: We demonstrated that exon 10 is predominantly included in nPTB transcripts consistent with nPTB protein in lenses, and that alternatively spliced Fox-1/-2 lens transcripts contain exons that have been considered neuron-specific. We identified a 3' alternative Fox-1 exon in lenses that encodes a nuclear localization signal consistent with its protein distribution detected in fiber cells. Neuronal alternative splicing of kinesin KIF1Bβ2 has been associated with PTB/nPTB and Fox-2, and we found that two 'neuron-specific' exons are also included in lenses. CONCLUSIONS: The present study provides evidence that alternative neuronal nPTB and Fox-1/Fox-2 isoforms are also produced in lenses. These findings raise questions regarding the extent these factors contribute to a similar reprogramming of alternative splicing during lens differentiation, and the degree that alternative gene transcripts produced during neurogenesis are also expressed in the lens.
Authors: Mohammed Farooq; Rajesh H Kaswala; Norman J Kleiman; Chinnaswamy Kasinathan; Peter H Frederikse Journal: Biochem Biophys Res Commun Date: 2012-01-10 Impact factor: 3.575
Authors: Dwight Stambolian; Robert Wojciechowski; Konrad Oexle; Mario Pirastu; Xiaohui Li; Leslie J Raffel; Mary Frances Cotch; Emily Y Chew; Barbara Klein; Ronald Klein; Tien Y Wong; Claire L Simpson; Caroline C W Klaver; Cornelia M van Duijn; Virginie J M Verhoeven; Paul N Baird; Veronique Vitart; Andrew D Paterson; Paul Mitchell; Seang Mei Saw; Maurizio Fossarello; Krista Kazmierkiewicz; Federico Murgia; Laura Portas; Maria Schache; Andrea Richardson; Jing Xie; Jie Jin Wang; Elena Rochtchina; Ananth C Viswanathan; Caroline Hayward; Alan F Wright; Ozren Polasek; Harry Campbell; Igor Rudan; Ben A Oostra; André G Uitterlinden; Albert Hofman; Fernando Rivadeneira; Najaf Amin; Lennart C Karssen; Johannes R Vingerling; S M Hosseini; Angela Döring; Thomas Bettecken; Zoran Vatavuk; Christian Gieger; H-Erich Wichmann; James F Wilson; Brian Fleck; Paul J Foster; Fotis Topouzis; Peter McGuffin; Xueling Sim; Michael Inouye; Elizabeth G Holliday; John Attia; Rodney J Scott; Jerome I Rotter; Thomas Meitinger; Joan E Bailey-Wilson Journal: Hum Mol Genet Date: 2013-03-07 Impact factor: 6.150