Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

ABSTRACT: Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G₄C₂ construct was placed as the second cistron in a bi

SUBMITTER: Sonobe Y 

PROVIDER: S-EPMC6331062 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature