RNA association and nucleocytoplasmic shuttling by ataxin-1

J Cell Sci. 2005 Jan 1;118(Pt 1):233-42. doi: 10.1242/jcs.01611.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ataxin-1
  • Ataxins
  • Biological Transport
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism*
  • Fluorescence Recovery After Photobleaching
  • Fluorescent Antibody Technique, Indirect
  • Fluorescent Dyes
  • HeLa Cells
  • Humans
  • Image Processing, Computer-Assisted
  • Kinetics
  • Mice
  • Microscopy, Confocal
  • Mutation
  • NIH 3T3 Cells
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organic Chemicals
  • RNA / metabolism*

Substances

  • ATXN1 protein, human
  • Alexa594
  • Ataxin-1
  • Ataxins
  • Atxn1 protein, mouse
  • Fluorescent Dyes
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Organic Chemicals
  • RNA