Repeat-associated non-ATG (RAN) translation

Abstract

Microsatellite expansions cause more than 40 neurological disorders, including Huntington's disease, myotonic dystrophy, and C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). These repeat expansion mutations can produce repeat-associated non-ATG (RAN) proteins in all three reading frames, which accumulate in disease-relevant tissues. There has been considerable interest in RAN protein products and their downstream consequences, particularly for the dipeptide proteins found in C9ORF72 ALS/FTD. Understanding how RAN translation occurs, what cellular factors contribute to RAN protein accumulation, and how these proteins contribute to disease should lead to a better understanding of the basic mechanisms of gene expression and human disease.

Keywords: C9ORF72 ALS/FTD; Huntington's disease; RAN translation; amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease); mouse models; myotonic dystrophy; nucleocytoplasmic transport; spinocerebellar ataxia; translation; translation initiation; trinucleotide repeat disease.