Repeat-associated non-ATG (RAN) translation

J Biol Chem. 2018 Oct 19;293(42):16127-16141. doi: 10.1074/jbc.R118.003237. Epub 2018 Sep 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • C9orf72 Protein
  • DNA Repeat Expansion*
  • Dipeptides
  • Frontotemporal Dementia / genetics
  • Gene Expression
  • Huntington Disease / genetics
  • Microsatellite Repeats*
  • Mutation
  • Myotonic Dystrophy / genetics
  • Nervous System Diseases / genetics*


  • C9orf72 Protein
  • C9orf72 protein, human
  • Dipeptides

Supplementary concepts

  • Frontotemporal Dementia With Motor Neuron Disease