Translational Suppression by Trinucleotide Repeat Expansion at FMR1
Abstract
Fragile X syndrome is the result of the unstable expansion of a trinucleotide repeat in the 5'-untranslated region of the FMR1 gene. Fibroblast subclones from a mildly affected patient, each containing stable FMR1 alleles with 57 to 285 CGG repeats, were shown to exhibit normal steady-state levels of FMR1 messenger RNA. However, FMR protein was markedly diminished from transcript with more than 200 repeats. Such transcripts were associated with stalled 40S ribosomal subunits. These results suggest that a structural RNA transition beyond 200 repeats impedes the linear 40S migration along the 5'-untranslated region. This results in translational inhibition by trinucleotide repeat expansion.
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Premutations appear to influence translation of FMR1 mRNA.
“Premutations do appear however to influence translation of FMR1 mRNA (Feng et al., 1995).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Feng et al., 1995
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- Authors
- Feng, Y., Zhang, F., Lokey, L. K., Chastain, J. L., Lakkis, L., Eberhart, D., & Warren, S. T.
- Affiliations
- Emory University (US)
- Venue
- Science
- Published
- 1995-05-05
- Volume
- 268
- Issue
- 5211
- Pages
- 731-734
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2040118711
- Cited by
- 358
- References
- 40
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 6 · 2014: 12 · 2013: 6 · 2012: 19
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 20521)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- fragile X syndrome, FMR1 gene, trinucleotide repeat expansion, CGG repeat, 5' untranslated region, translational suppression, FMRP, 40S ribosomal subunit, ribosome stalling, RNA secondary structure
- MeSH terms
- Centrifugation, Density Gradient, Clone Cells, Female, Fibroblasts, Fragile X Syndrome, Humans, Infant, Male, Nerve Tissue Proteins, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Protein Biosynthesis, Down-Regulation, Polymerase Chain Reaction, RNA-Binding Proteins, Fragile X Messenger Ribonucleoprotein 1
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