Abstract
People with 59-200 CGG.CCG-repeats in the 5' UTR of one of their FMR1 genes are at risk for Fragile X tremor and ataxia syndrome. Females are also at risk for premature ovarian failure. These symptoms are thought to be due to the presence of the repeats at the DNA and/or RNA level. We show here that long transcribed but untranslated CGG-repeat tracts are toxic to human cells and alter the expression of a wide variety of different genes including caspase-8, CYFIP, Neurotensin and UBE3A.
MeSH terms
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5' Untranslated Regions
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Alleles*
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Annexin A5 / drug effects
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Annexin A5 / metabolism
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Ataxia / genetics
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Blotting, Western
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Caspase 8
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Caspases / analysis
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Caspases / genetics
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Caspases / metabolism
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Cell Line
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Cell Survival
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Culture Media, Serum-Free
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Dose-Response Relationship, Drug
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Doxycycline / pharmacology
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Female
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Fragile X Syndrome / genetics*
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Gene Expression Profiling
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Gene Expression Regulation
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Herbicides / pharmacology
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Heterozygote*
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Humans
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Mutation
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Neurotensin / genetics
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Neurotensin / metabolism
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Oligonucleotide Array Sequence Analysis
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Paraquat / pharmacology
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Staurosporine / pharmacology
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Trinucleotide Repeat Expansion / drug effects*
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Trinucleotide Repeat Expansion / genetics
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism
Substances
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5' Untranslated Regions
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Adaptor Proteins, Signal Transducing
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Annexin A5
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CYFIP1 protein, human
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Culture Media, Serum-Free
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Herbicides
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Neurotensin
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UBE3A protein, human
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Ubiquitin-Protein Ligases
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CASP8 protein, human
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Caspase 8
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Caspases
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Staurosporine
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Doxycycline
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Paraquat