Skip Navigation



Human Molecular Genetics Advance Access published online on June 10, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp278
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
18/18/3384    most recent
ddp278v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Suraweera, A.
Right arrow Articles by Lavin, M. F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suraweera, A.
Right arrow Articles by Lavin, M. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation

Amila Suraweera1, YiChieh Lim1,2, Rick Woods1, Geoff W. Birrell1, Talat Nasim3, Olivier J. Becherel1 and Martin F. Lavin1,2,*

1 Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia 2 University of Queensland, Centre for Clinical Research, QLD 4029, Australia 3 Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London SE1 9RT, UK

* Corresponding author: Prof. Martin F. Lavin Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, QLD 4029, Australia, Tel: +61(0)7-3362-0341, Fax: +61(0)7-3362-0106, e-mail: Martin.Lavin{at}qimr.edu.au

Received January 30, 2009; Revised May 19, 2009; Accepted June 8, 2009

Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role in the response to oxidative stress. To investigate further the function of senataxin, we identified novel senataxin interacting proteins, the majority of which are involved in transcription and RNA processing, including RNA polymerase II. Binding of RNA polymerase II to candidate genes was significantly reduced in senataxin deficient cells and this was accompanied by decreased transcription of these genes, suggesting a role for senataxin in the regulation/modulation of transcription. RNA polymerase II-dependent transcription termination was defective in cells depleted of senataxin in keeping with the observed interaction of senataxin with poly(A) binding proteins 1 and 2. Splicing efficiency of specific mRNAs and alternate splice-site selection of both endogenous genes and artificial minigenes were altered in senataxin depleted cells. These data suggest that senataxin, similar to its yeast homolog Sen1p, plays a role in coordinating transcriptional events, in addition to its role in DNA repair.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.