PMID: 25725227Mar 1, 2015Paper

Unwinding the role of senataxin in neurodegeneration

Discovery Medicine
C L Bennett, Albert R La Spada

Abstract

Interest in senataxin biology began in 2004 when mutations were first identified in what was then a novel protein. Dominantly inherited mutations were documented in rare juvenile-onset, motor neuron disease pedigrees in a familial form of amyotrophic lateral sclerosis (ALS4), while recessive mutations were found to cause a severe early-onset ataxia with oculomotor apraxia (AOA2) that is actually the second most common recessive ataxia after Freidreich's ataxia. From earlier studies of sen1p, the yeast ortholog of senataxin, a range of important RNA processing functions have been attributed to this protein. Like sen1p, senataxin contains a helicase domain to interact with RNA and an amino-terminal domain for critical protein interactions. Senataxin also joins a group of important proteins responsible for maintaining RNA transcriptome homeostasis, including FUS, TDP-43, and SMN that can all cause familial forms of motor neuron disease (MND). Independent of this association, senataxin is gaining attention for its role in maintaining genomic stability. Senataxin has been shown to resolve R-Loop structures, which form when nascent RNA hybridizes to DNA, displacing the non-transcribed strand. But in cycling cells, senataxin is also f...Continue Reading

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