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Reduced FMR1 mRNA translation efficiency in Fragile X patients with premutations

Published online by Cambridge University Press:  16 January 2003

BEATRICE PRIMERANO ,
FLORA TASSONE ,
RANDI J. HAGERMAN ,
PAUL HAGERMAN ,
FRANCESCO AMALDI  and
CLAUDIA BAGNI
BEATRICE PRIMERANO
Affiliation:
Dipartimento di Biologia, Università di Roma “Tor Vergata,” 00133 Roma, Italy
FLORA TASSONE
Affiliation:
Department of Biological Chemistry, University of California, Davis, California 95616, USA
RANDI J. HAGERMAN
Affiliation:
The M.I.N.D. Institute, University of California–Davis Medical Center, Sacramento, California 95616, USA
PAUL HAGERMAN
Affiliation:
Department of Biological Chemistry, University of California, Davis, California 95616, USA
FRANCESCO AMALDI
Affiliation:
Dipartimento di Biologia, Università di Roma “Tor Vergata,” 00133 Roma, Italy
CLAUDIA BAGNI
Affiliation:
Dipartimento di Biologia, Università di Roma “Tor Vergata,” 00133 Roma, Italy
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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.

Keywords

FRAXAmental retardationmRNA translationrepeat expansion
Type
REPORT
Information
RNA , Volume 8 , Issue 12 , December 2002 , pp. 1482 - 1488
Copyright
2002 RNA Society

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