The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by the expansion of a polyglutamine tract within the SCA1 product, ataxin-1. Previously, using transgenic mice, it was demonstrated that in order for a mutant allele of ataxin-1 to cause disease it must be transported to the nucleus of the neuron. Using an in vitro RNA-binding assay, we demonstrate that ataxin-1 does bind RNA and that this binding diminishes as the length of its polyglutamine tract increases. These observations suggest that ataxin-1 plays a role in RNA metabolism and that the expansion of the polyglutamine tract may alter this function.
Yue
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Institute of Human Genetics, Department of Laboratory Medicine and Pathology, Mayo Mail Code 206, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Serra
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Zoghbi
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Orr
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D000067696:Ataxin-1; D000067528:Ataxins; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000378:metabolism*; D014158:Transcription, Genetic
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine; D012313:RNA