Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes.
The fragile X mental retardation syndrome is caused by large methylated expansions of a CGG repeat in the FMR1 gene that lead to the loss of expression of FMRP, an RNA-binding protein. FMRP is proposed to act as a regulator of mRNA transport or translation that plays a role in synaptic maturation and function. The recent observations of unexpected phenotypes in some carriers of fragile X premutations suggest a pathological role, in these individuals, of an abnormal FMR1 mRNA. FMRP was recently shown to interact preferentially with mRNAs containing a G quartet structure. Mouse and Drosophila models are used to decipher the function of FMRP, which was found to inhibit translation of some mRNA targets, but may be stimulatory in other cases. Proteins interacting with FMRP have been identified, and suggest a link with the Rac1 GTPase pathway that is important in neuronal maturation. Recent advances also include identification of other genes implicated in X-linked mental retardation.
Bardoni
Barbara
B
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163, 67404 Illkirch cedex, CU de Strasbourg, France.
Mandel
Jean-Louis
JL
D001921:Brain / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016601:RNA-Binding Proteins; D019680:Trinucleotide Repeat Expansion; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D020741:rho GTP-Binding Proteins; C497683:FMR1 protein, human