title: Friedreich's ataxia--a case of aberrant transcription termination?
abstract: Reduced expression of the mitochondrial protein Frataxin (FXN) is the underlying cause of Friedreich's ataxia. We propose a model of premature termination of FXN transcription induced by pathogenic expanded GAA repeats that links R-loop structures, antisense transcription, and heterochromatin formation as a novel mechanism of transcriptional repression in Friedreich's ataxia.
authors.affiliation: a University of Alabama at Birmingham; Department of Biochemistry and Molecular Genetics ; UAB Stem Cell Institute ; Birmingham , AL USA.
authors.forename: Jill Sergesketter
authors.initials: JS
authors.lastname: Butler
authors.forename: Marek
authors.initials: M
authors.lastname: Napierala
mesh_terms: D005621:Friedreich Ataxia / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000235:genetics; D006801:Humans; D033862:Iron-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D008928:Mitochondria / Q000235:genetics; D061806:Transcription Termination, Genetic; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D000096923:Frataxin
chemical_list: D006570:Heterochromatin; D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: FRDA, Friedreich's ataxia; FXN, Frataxin; Friedreich's ataxia; GAA repeats; H3K9me2/me3, histone H3 lysine 9 methylation; PAS, polyadenylation signal; R-loops; RNAP II, RNA polymerase II; UTRs, untranslated regions; antisense transcription; dsRNA, double-stranded RNA; repeat expansion diseases; transcription termination
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