Reconstitution of C9orf72 GGGGCC repeat-associated non-AUG translation with purified human translation factors.

Nucleotide repeat expansion of GGGGCC (GC) in the non-coding region of C9orf72 is the most common genetic cause underlying amyotrophic lateral sclerosis and frontotemporal dementia. Transcripts harboring this repeat expansion undergo the translation of dipeptide repeats via a non-canonical process known as repeat-associated non-AUG (RAN) translation. In order to ascertain the essential components required for RAN translation, we successfully recapitulated GC-RAN translation using an in vitro reconstituted translation system comprising human factors, namely the human PURE system.