Discovery of a mutation-containing circRNA in polyglutamine disease through systematic analysis of RNAs with CAG repeats.

CAG repeat tracts occur in both non-coding and translated RNAs, have tended to lengthen throughout evolution, and are thought to enhance neuronal function. We identified over 600 human RNAs (including mRNAs, lncRNAs, and circRNAs) with at least 10 CAG repeats, originating from 58 genomic loci, which vary, e.g. in the rate of CAG length polymorphism. Several circRNAs originate from the ATXN7 locus, where CAG expansion causes spinocerebellar ataxia type 7 (SCA7). For selected circATXN7(3,4).1 (circ1), we demonstrated its cytoplasmic localization, as well as its presence in 40S, monosome and polysome fractions. We showed that circ1 is expressed in human fibroblasts, blood and cerebellum, and, importantly, we identified a mutation-containing circRNA with potential implications in SCA7.