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

Suraweera, Amila, Lim, YiChieh, Woods, Rick, Birrell, Geoff W., Nasim, Talat, Becherel , Olivier J., & Lavin, Martin F. (2009) Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation. Human Molecular Genetics, 18(18), pp. 3384-3396.

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Abstract

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.

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ID Code: 74594
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
DOI: 10.1093/hmg/ddp278
ISSN: 1460-2083
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2009 Oxford University Press
Deposited On: 31 Jul 2014 23:03
Last Modified: 30 Jan 2015 05:06

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