title: New developments in RAN translation: insights from multiple diseases.
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.
authors.affiliation: Center for NeuroGenetics, University of Florida, Gainesville, FL, USA; Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA; Genetics Institute, University of Florida, Gainesville, FL, USA.
authors.forename: John Douglas
authors.initials: JD
authors.lastname: Cleary
authors.affiliation: Center for NeuroGenetics, University of Florida, Gainesville, FL, USA; Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Neurology, University of Florida, Gainesville, FL, USA; Genetics Institute, University of Florida, Gainesville, FL, USA; McKnight Brain Institute, University of Florida, Gainesville, FL, USA. Electronic address: ranum@ufl.edu.
authors.forename: Laura Pw
authors.initials: LP
authors.lastname: Ranum
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D000073885:C9orf72 Protein / Q000235:genetics; D018387:Codon, Initiator / Q000235:genetics; D042622:DNA Repeat Expansion / Q000235:genetics*; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000503:physiopathology; D016366:Open Reading Frames / Q000235:genetics; D014176:Protein Biosynthesis
chemical_list: D000073885:C9orf72 Protein; D018387:Codon, Initiator; D050505:Mutant Proteins