Translation of the poly(GR) frame in C9ORF72-ALS/FTD is regulated by cis-elements involved in alternative splicing.

ABSTRACT: GGGGCC (G₄C₂) repeat expansion in the first intron of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia, two devastating age-dependent neurodegenerative disorders. Both sense and antisense repeat RNAs can be translated into 5 different dipeptide repeat proteins, such as poly(GR), which is toxic in various cellular and animal models. However, it remains unknown how poly(GR) is synthesized in patient neurons. Using a reporter construct containing 70 G₄C₂ repeats flanked by human intronic and exonic sequences, we show that translation of the poly(GR) frame does not depend on repeats or the CUG start codon in the poly(GA) frame, suggesting poly(GR) is not produced after ribosomal frameshifting in th

SUBMITTER: Lampasona A 

PROVIDER: S-EPMC8338774 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature