CCG•CGG interruptions in high‐penetrance SCA8 families increase RAN translation and protein toxicity [PDF]
EMBO Molecular Medicine, 2021 Spinocerebellar ataxia type 8 (SCA8), a dominantly inherited neurodegenerative disorder caused by a CTG•CAG expansion, is unusual because most individuals that carry the mutation do not develop ataxia.
Barbara A Perez +18 more
doaj +6 more sources
A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis [PDF]
Nature Neuroscience, 2020 Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5'-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In
Marius F Ifrim +2 more
exaly +6 more sources
RAN Translation in Huntington Disease [PDF]
Neuron, 2015 Huntington disease (HD) is caused by a CAG ⋅ CTG expansion in the huntingtin (HTT) gene. While most research has focused on the HTT polyGln-expansion protein, we demonstrate that four additional, novel, homopolymeric expansion proteins (polyAla, polySer, polyLeu, and polyCys) accumulate in HD human brains.
Mónica Bañez-Coronel +2 more
exaly +5 more sources
RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2 [PDF]
Neuron, 2017 Several microsatellite-expansion diseases are characterized by the accumulation of RNA foci and RAN proteins, raising the possibility of a mechanistic connection. We explored this question using myotonic dystrophy type 2, a multisystemic disease thought to be primarily caused by RNA gain-of-function effects.
Tao Zu +2 more
exaly +6 more sources
New developments in RAN translation: insights from multiple diseases [PDF]
Current Opinion in Genetics and Development, 2017 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.
Laura P W Ranum
exaly +6 more sources
FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD [PDF]
eLife, 2023 Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD).
Yuzo Fujino +28 more
doaj +2 more sources
RAN Translation of the Expanded CAG Repeats in the SCA3 Disease Context [PDF]
Journal of Molecular Biology, 2020 Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the ATXN3 gene encoding the ataxin-3 protein. Despite extensive research the exact pathogenic mechanisms of SCA3 are still not understood in depth.
Adam Ciesiolka +2 more
exaly +4 more sources
Repeat-associated non-AUG (RAN) translation: insights from pathology. [PDF]
Lab Invest, 2019 More than 40 different neurological diseases are caused by microsatellite repeat expansions. Since the discovery of repeat-associated non-AUG (RAN) translation by Zu et al. in 2011, nine expansion disorders have been identified as RAN-positive diseases. RAN proteins are translated from different types of nucleotide repeat expansions and can be produced
Banez-Coronel M, Ranum LPW.
europepmc +4 more sources
A C. elegans model of C9orf72-associated ALS/FTD uncovers a conserved role for eIF2D in RAN translation [PDF]
Nature Communications, 2021 A hexanucleotide repeat expansion of C9orf72 is translated to dipeptide repeat proteins in amyotrophic lateral sclerosis and frontotemporal dementia patients. Here the authors generate a C.
Yoshifumi Sonobe +14 more
doaj +2 more sources
RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders. [PDF]
Nucleic Acids Res, 2014 Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation ...
Wojciechowska M +4 more
europepmc +4 more sources