Translational Suppression by Trinucleotide Repeat Expansion at FMR1
- 5 May 1995
- journal article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 268 (5211) , 731-734
- https://doi.org/10.1126/science.7732383
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.Keywords
This publication has 37 references indexed in Scilit:
- Molecular cytogenetic study of supernumerary marker chromosomes in an unselected group childrenAmerican Journal of Medical Genetics, 1995
- Triplet Repeat Expansion Mutations: The Example of Fragile X SyndromeAnnual Review of Neuroscience, 1995
- Dynamic mutations hit double figuresNature Genetics, 1994
- Precursor arrays for triplet repeat expansion at the fragile X locusHuman Molecular Genetics, 1994
- Sequence analysis of the fragile X trinucleotide repeat: implications for the origin of the fragile X mutationHuman Molecular Genetics, 1994
- Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG–repeatNature Genetics, 1993
- Molecular studies of the fragile X syndromeAmerican Journal of Medical Genetics, 1992
- Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradoxCell, 1991
- Absence of expression of the FMR-1 gene in fragile X syndromeCell, 1991
- Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndromePublished by Elsevier ,1991