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Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation
- Source :
- Human Molecular Genetics
- Publication Year :
- 2009
-
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.
- Subjects :
- Cerebellar Ataxia
DNA Repair
Transcription, Genetic
RNA polymerase II
chemistry.chemical_compound
Transcription (biology)
RNA interference
RNA polymerase
Genetics
Transcriptional regulation
Oculomotor Nerve Diseases
RNA Precursors
Humans
Molecular Biology
Gene
Genetics (clinical)
060100 BIOCHEMISTRY AND CELL BIOLOGY
060400 GENETICS
biology
DNA Helicases
RNA
General Medicine
DNA
RNA Helicase A
Multifunctional Enzymes
110100 MEDICAL BIOCHEMISTRY AND METABOLOMICS
Alternative Splicing
chemistry
Gene Expression Regulation
biology.protein
RNA Helicases
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 14602083
- Volume :
- 18
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Human molecular genetics
- Accession number :
- edsair.doi.dedup.....e1100f34f3effea3749e6b3c28df172a