Premature transcription termination at the expanded GAA repeats and aberrant alternative polyadenylation contributes to the Frataxin transcriptional deficit in Friedreich’s ataxia

Yanjie Li, Jixue Li, Jun Wang, Siyuan Zhang, Keith Giles, Thazha P Prakash, Frank Rigo, Jill S Napierala, Marek Napieral; Human Molecular Genetics, 2022;, ddac134, doi:10.1093/hmg/ddac134 

The level the FXN-ett RNA directly correlates with the length of the longer of the two expanded GAA tracts. Targeting GAAs with antisense oligonucleotides or excision of the repeats eliminates the transcription impediment, diminishes expression of the aberrant FXN-ett, while increasing levels of FXN mRNA and frataxin. Non-productive transcription may represent a common phenomenon and attractive therapeutic target in diseases caused by repeat-mediated transcription aberrations.

Premature transcription termination at the expanded GAA repeats and aberrant alternative polyadenylation contributes to the Frataxin transcriptional deficit in Friedreich’s ataxia