Evidence That 'Brain-Specific' Fox-1, Fox-2, and nPTB Alternatively Spliced Isoforms Are Produced 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, conta...

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Published in:	Current eye research Vol. 36; no. 4; pp. 321 - 327
Main Authors:	Bitel, Claudine L., Nathan, Rachel, Wong, Patrick, Kuppasani, Sunil, Matsushita, Masafumi, Kanazawa, Hrioshi, Frederikse, Peter H.
Format:	Journal Article
Language:	English
Published:	England Informa Healthcare 01-04-2011 Taylor & Francis
Subjects:	Alternative Splicing Amino Acid Sequence Animals Base Sequence Brain - metabolism Exons - genetics Fluorescent Antibody Technique, Indirect Fox-1 Gene Expression Regulation - physiology Immunoblotting Kinesin - genetics Lens Lens, Crystalline - metabolism Mice Mice, Inbred C57BL Molecular Sequence Data Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Polypyrimidine tract binding proteins Polypyrimidine Tract-Binding Protein - genetics Polypyrimidine Tract-Binding Protein - metabolism Protein Isoforms - genetics Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction RNA binding proteins RNA Splicing - genetics RNA Splicing Factors RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0271-3683 1460-2202
DOI:	10.3109/02713683.2010.500114