Abstract |
Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co-immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX-2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1.
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Authors | Franziska Welzel, Christian Kaehler, Melanie Isau, Linda Hallen, Hans Lehrach, Sylvia Krobitsch |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 5
Pg. e37985
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22666429
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATXN1 protein, human
- Ataxin-1
- Ataxins
- Nerve Tissue Proteins
- Nuclear Proteins
- Protein Isoforms
- RBFOX2 protein, human
- RNA Splicing Factors
- RNA, Messenger
- RNA-Binding Proteins
- Repressor Proteins
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Topics |
- Alternative Splicing
- Ataxin-1
- Ataxins
- Cell Nucleus
(metabolism)
- Gene Expression Regulation
(genetics)
- HEK293 Cells
- HeLa Cells
- Humans
- Nerve Tissue Proteins
(genetics)
- Nuclear Proteins
(genetics)
- Protein Binding
- Protein Isoforms
(metabolism)
- Protein Transport
- RNA Splicing Factors
- RNA, Messenger
(genetics, metabolism)
- RNA-Binding Proteins
(metabolism)
- Repressor Proteins
(metabolism)
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