RNA Editing and Retrotransposons in Neurology

Heinz Krestel and Jochen C. Meier;  Front Mol Neurosci. 2018; 11: 163. doi:10.3389/fnmol.2018.00163

Friedreich ataxia is the best known and most commonly inherited form of spinocerebellar ataxia. It can be caused by mutations or, in 98% of cases, by GAA trinucleotide-repeat expansions located at the center of an AluSq element in intron 1 of the frataxin (FXN) gene. Friedreich ataxia is the only known disease caused by abnormal expansion of a GAA trinucleotide-repeat sequence. It was suggested that GAA repeats arose by mutation or A-to-G conversion from poly(A) tracts of Alu elements. Many longer GAA repeats in the human genome can be found in the 3′ poly(A) tracts of Alu elements, but it was suggested that A-to-G conversion that led to poly-GAA repeats in Friedreich ataxia arose in the central linker region of Alu elements. Beyond GAA repeats, Alu elements were in general described to be a source for microsatellites. Expansion of trinucleotide repeats was proposed to have arisen in Friedreich ataxia rather by in-tandem duplication up to a certain repeat length. From a certain repeat length onwards, genetic instability was proposed to contribute to additional repeat expansion, which is known in Neurology as anticipation. GAA repeat expansions affect pre-mRNA processing by inducing the accumulation of upstream splicing intermediates. No interaction of RNA editing with these genetic rearrangements in Friedreich ataxia has been reported.

 RNA Editing and Retrotransposons in Neurology