The Fragile X mental retardation ′gene (FMR1) contains a polymorphic trinucleotide CGG repeat in the 5 untranslated region (UTR) of the FMR1 messenger. We have characterized three lymphoblastoid cell lines derived from unrelated male carriers of a premutation that overexpress FMR1 mRNA and show reduced FMRP level compared to normal cells. The analysis of polysomes/mRNPs distribution of mRNA in the cell lines with a premutation shows that the polysomal association of FMR1 mRNA, which is high in normal cells, becomes progressively lower with increasing CGG repeat expansion. In addition, we could detect a very low level of FMR1 mRNA in a lymphoblastoid cell line from a patient with a full mutation. In this case, FMR1 mRNA is not at all associated with polysomes, in agreement with the complete absence of FMRP. The impairment of FMR1 mRNA translation in patients with the Fragile X syndrome with FMR1 premutation is the cause of the lower FMRP levels that leads to the clinical involvement.

Primerano, B., Tassone, F., Hagerman, R.J., Hagerman, P., Amaldi, F., & Bagni, C. (2002). Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations. RNA, 8(12), 1482-1488 [10.1017/S1355838202020642].

Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations

AMALDI, FRANCESCO;BAGNI, CLAUDIA
2002

Abstract

The Fragile X mental retardation ′gene (FMR1) contains a polymorphic trinucleotide CGG repeat in the 5 untranslated region (UTR) of the FMR1 messenger. We have characterized three lymphoblastoid cell lines derived from unrelated male carriers of a premutation that overexpress FMR1 mRNA and show reduced FMRP level compared to normal cells. The analysis of polysomes/mRNPs distribution of mRNA in the cell lines with a premutation shows that the polysomal association of FMR1 mRNA, which is high in normal cells, becomes progressively lower with increasing CGG repeat expansion. In addition, we could detect a very low level of FMR1 mRNA in a lymphoblastoid cell line from a patient with a full mutation. In this case, FMR1 mRNA is not at all associated with polysomes, in agreement with the complete absence of FMRP. The impairment of FMR1 mRNA translation in patients with the Fragile X syndrome with FMR1 premutation is the cause of the lower FMRP levels that leads to the clinical involvement.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11
English
Con Impact Factor ISI
FRAXA; Mental retardation; mRNA translation; Repeat expansion
Primerano, B., Tassone, F., Hagerman, R.J., Hagerman, P., Amaldi, F., & Bagni, C. (2002). Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations. RNA, 8(12), 1482-1488 [10.1017/S1355838202020642].
Primerano, B; Tassone, F; Hagerman, R; Hagerman, P; Amaldi, F; Bagni, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/48131
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