Cited by 358Genetics and Neurodevelopmental DisordersRNA and protein synthesis mechanismsGenetic Neurodegenerative Diseases

Translational Suppression by Trinucleotide Repeat Expansion at FMR1

Feng, Yue, Zhang, Fuping, Lokey, Laurie K., Chastain, Jane L., Lakkis, Lisa, Eberhart, Derek, Warren, Stephen T.·1995·Science

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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Crossref · 10.1126/science.7732383

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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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