New developments in RAN translation: insights from multiple diseases

Curr Opin Genet Dev. 2017 Jun;44:125-134. doi: 10.1016/j.gde.2017.03.006. Epub 2017 Mar 30.

Abstract

Since the discovery of repeat-associated non-ATG (RAN) translation, and more recently its association with amyotrophic lateral sclerosis/frontotemporal dementia, there has been an intense focus to understand how this process works and the downstream effects of these novel proteins. RAN translation across several different types of repeat expansions mutations (CAG, CTG, CCG, GGGGCC, GGCCCC) results in the production of proteins in all three reading frames without an ATG initiation codon. The combination of bidirectional transcription and RAN translation has been shown to result in the accumulation of up to six mutant expansion proteins in a growing number of diseases. This process is complex mechanistically and also complex from the perspective of the downstream consequences in disease. Here we review recent developments in RAN translation and their implications on our basic understanding of neurodegenerative disease and gene expression.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • C9orf72 Protein / genetics
  • Codon, Initiator / genetics
  • DNA Repeat Expansion / genetics*
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / physiopathology
  • Humans
  • Mutant Proteins / genetics*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology
  • Open Reading Frames / genetics
  • Protein Biosynthesis*

Substances

  • C9orf72 Protein
  • Codon, Initiator
  • Mutant Proteins

Supplementary concepts

  • Frontotemporal Dementia With Motor Neuron Disease