Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations.
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
Beatrice
B
Dipartimento di Biologia, Università di Roma Tor Vergata, 00133 Roma, Italy.
Tassone
Flora
F
Hagerman
Randi J
RJ
Hagerman
Paul
P
Amaldi
Francesco
F
Bagni
Claudia
C
D002460:Cell Line; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D019680:Trinucleotide Repeat Expansion
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human