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Author Notes:

Corresponding author: Peng Jin, Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America. Email: peng.jin@emory.edu.

Conceived and designed the experiments: PJ AQ.

Performed the experiments: AQ WL J-YZ.

Analyzed the data: AQ JP PJ.

Contributed reagents/materials/analysis tools: JP PJ.

Wrote the paper: AQ PJ.

The authors would like to thank A. Spradling, F. Fuller-Pace, E. Lei, and M. Ramaswami for providing useful reagents and J. Taylor of The Integrated Microscopy and Microanalytical Facility for their help with SEM.

The authors would also like to thank the members of the Jin lab for their assistance and C. Strauss for critical reading of the manuscript.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects:

Research Funding:

AQ was supported by and is a recipient of a National Ataxia Postdoctoral Award.

PJ is supported by NIH grants R01 NS051630 and R01 MH076090.

PJ is a recipient of the Beckman Young Investigator Award and the Basil O'Connor Scholar Research Award, as well as an Alfred P. Sloan Research Fellow in Neuroscience.

JP is funded by NIH grants (P50AG025688 and P30NS055077).

Nuclear Accumulation of Stress Response mRNAs Contributes to the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats

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Journal Title:

PLoS Genetics

Volume:

Volume 7, Number 6

Publisher:

, Pages e1002102-e1002102

Type of Work:

Article | Final Publisher PDF

Abstract:

Fragile X–associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that usually affects males over 50 years of age, and FXTAS patients are carriers of fragile X premutation alleles. Using a FXTAS Drosophila model, we previously showed that fragile X premutation rCGG repeats alone could cause neurodegeneration. Pur α and hnRNP A2/B1 were identified as specific premutation rCGG repeat-binding proteins (RBPs) that could bind and modulate fragile X premutation rCGG–mediated neuronal degeneration. Here, through systematic proteomic, genetic, and microarray analyses, we show that the nuclear accumulation of select mRNAs caused by fragile X premutation rCGG repeats may contribute to FXTAS pathogenesis, and the mechanism could be via impaired nuclear export due to the decreased levels of Rm62 seen upon fragile X premutation rCGG expression.

Copyright information:

© 2011 Qurashi et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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