Repeat associated non-ATG (RAN) translation: new starts in microsatellite expansion disorders.
Microsatellite-expansion diseases are a class of neurological and neuromuscular disorders caused by the expansion of short stretches of repetitive DNA (e.g. GGGGCC, CAG, CTG …) within the human genome. Since their discovery 20 years ago, research into how microsatellites expansions cause disease has been examined using the model that these genes are expressed in one direction and that expansion mutations only encode proteins when located in an ATG-initiated open reading frame. The fact that these mutations are often bidirectionally transcribed combined with the recent discovery of repeat associated non-ATG (RAN) translation provides new perspectives on how these expansion mutations are expressed and impact disease. Two expansion transcripts and a set of unexpected RAN proteins must now be considered for both coding and 'non-coding' expansion disorders. RAN proteins have been reported in a growing number of diseases, including spinocerebellar ataxia type 8 (SCA8), myotonic dystrophy type 1 (DM1), Fragile-X tremor ataxia syndrome (FXTAS), and C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD).
Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA; Genetics Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
John Douglas
JD
Cleary
Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA; Genetics Institute, College of Medicine, University of Florida, Gainesville, FL, USA. Electronic address: ranum@ufl.edu.
Laura P W
LP
Ranum
D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics*; D042622:DNA Repeat Expansion / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics; D014176:Protein Biosynthesis; D013132:Spinocerebellar Degenerations / Q000235:genetics
D018387:Codon, Initiator; D050505:Mutant Proteins