Friedreich's ataxia – a case of aberrant transcription termination?

Friedreich's ataxia – a case of aberrant transcription termination?

Jill Sergesketter Butler and Marek Napierala

a University of Alabama at Birmingham,Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, 1825 University Blvd., Birmingham, Alabama35294, USAb Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences,Poznan, 61-704, Poland


Published online: 01 Apr 2015


Reduced expression of the mitochondrial protein Frataxin (FXN) is the underlying cause of Friedreich's ataxia. We propose a model of premature termination ofFXN 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.

Key words: Friedreich's ataxia,R-loops, antisense transcription, repeat expansion diseases, GAA repeats,transcription termination
Abbreviations and acronyms:Friedreich's ataxia (FRDA),Frataxin (FXN), histone H3 lysine 9 methylation (H3K9me2/me3), RNA polymerase II (RNAP II),double-stranded RNA (dsRNA), untranslated regions (UTRs), polyadenylation signal (PAS)