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First published online December 22, 2004
doi: 10.1242/10.1242/jcs.01611

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RNA association and nucleocytoplasmic shuttling by ataxin-1

¹ McMaster University, HSC 4H45, Department of Biochemistry, Hamilton, Ontario, L8N 3Z5, Canada
² Department of Laboratory Medicine and Pathology and the Institute of Human Genetics, University of Minnesota, MN 55455-0213, USA

^* Author for correspondence (e-mail: truantr{at}mcmaster.ca)

Accepted 26 October 2004

Spinocerebellar ataxia type 1 (SCA1) is a dominant neurodegenerative disease caused by the expression of mutant ataxin-1 containing an expanded polyglutamine tract. Ataxin-1 is a nuclear protein that localizes to punctate inclusions similar to neuronal nuclear inclusions seen in many polyglutamine expansion disease proteins. We demonstrate that ataxin-1 localization to inclusions and inclusion dynamics within the nucleus are RNA and transcription dependent, but not dependent on the polyglutamine tract. Ataxin-1 nuclear inclusions are distinct from other described nuclear bodies but recruit the mRNA export factor, TAP/NXF1, in a manner that is enhanced by cell heat shock. By FRAP protein dynamic studies in live cells, we found that wild-type, but not mutant, ataxin-1 was capable of nuclear export. These results suggest that the normal role of ataxin-1 may be in RNA processing, perhaps nuclear RNA export. Thus, nuclear retention of mutant ataxin-1 may be an important toxic gain of function in SCA1 disease.

Key words: Ataxin-1, Spinocerebellar ataxia type 1, RNA processing, Nuclear transport

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