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Science 5 May 1995:
Vol. 268. no. 5211, pp. 731 - 734
DOI: 10.1126/science.7732383
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Articles

Science, Vol 268, Issue 5211, 731-734
Copyright © 1995 by American Association for the Advancement of Science

articles

Translational suppression by trinucleotide repeat expansion at FMR1

Y Feng, F Zhang, LK Lokey, JL Chastain, L Lakkis, D Eberhart, and ST Warren

Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, GA 30322.

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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RNA-dominant diseases.
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The (CGG)n repeat element within the 5' untranslated region of the FMR1 message provides both positive and negative cis effects on in vivo translation of a downstream reporter.
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Quantitative analysis of DNA demethylation and transcriptional reactivation of the FMR1 gene in fragile X cells treated with 5-azadeoxycytidine.
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Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers.
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F Tassone, R J Hagerman, A K Taylor, and P J Hagerman (2001)
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Association between idiopathic premature ovarian failure and fragile X premutation.
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Hum. Reprod. 15, 197-202
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Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes.
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The Fragile X Syndrome Single Strand d(CGG)[IMAGE] Nucleotide Repeats Readily Fold Back to Form Unimolecular Hairpin Structures.
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The 5'-Untranslated Region of the FMR1 Message Facilitates Translation by Internal Ribosome Entry.
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