Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing.

Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing. Research Abstract Details 

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Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing. Abstract Text:

June Sun,Hongzhi Xu,Sandeep Negi,S H Subramony,Michael D Hebert,June Sun,Hongzhi Xu,Sandeep Negi,S H Subramony,Michael D Hebert,

Nuclear inclusions formed by proteins with expanded polyglutamine tracts are found in several neurodegenerative diseases. The effect of nuclear inclusions formed by these disease proteins on the functional organization of the nucleus is only partially understood. In particular, it is not known whether polyglutamine disease proteins disrupt the function of Cajal bodies, which are subnuclear domains that play a role in the biogenesis of small nuclear ribonucleoproteins (snRNPs). snRNPs are an integral part of the pre-mRNA splicing machinery, so it is possible that mutant proteins that alter Cajal body activity indirectly affect pre-mRNA splicing. Here, we evaluate three different polyglutamine disease proteins--ataxin-1, ataxin-3, and huntingtin--for their ability to disrupt Cajal body localization and reduce the splicing of an artificial reporter in HeLa cells. Consistent with previous observations, ataxin-1 inclusions do not drastically alter the localization of Cajal bodies. In contrast, ataxin-3 inclusions associate with this structure. Inclusions formed by a fragment of the huntingtin protein do not associate with Cajal bodies or PML bodies, another subnuclear domain. Among the three disease proteins, only ataxin-3 significantly decreases the splicing of an artificial reporter. These results support the hypothesis that different mutant proteins vary in their ability to disrupt nuclear organization and function.

Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing. Publishing Authors By Initials

J Sun,H Xu,S Negi,SH Subramony,MD Hebert,J Sun,H Xu,S Negi,SH Subramony,MD Hebert,

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Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neuroscience research

VOLUME: 85

Page Numbers: 2306-17

Journal Abbreviation: J. Neurosci. Res.

ISSN: 0360-4012

DAY: 15

MONTH: Aug

YEAR: 2007

Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Differential effects of polyglutamine proteins on nuclear organization and artificial reporter splicing.

AFFILIATION: Department of Neurology, The University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.

Country: United States

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MEDLINETA: J Neurosci Res

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