Human Molecular Genetics Advance Access published online on March 28, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl074
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1 Unité de Recherche en Génétique Humaine et Moléculaire, Centre de recherche Hôpital Saint-François d'Assise, le CHUQ, Québec G1L 3L5; Département de biologie médicale, Faculté de médecine, Université Laval, Québec, Canada
* To whom correspondence should be addressed. The Fragile X syndrome, the leading cause of inherited mental retardation, is due to the inactivation of the Fragile Mental Retardation 1 gene (FMR1) and the subsequent absence of its gene product FMRP. This RNA-binding protein is thought to control mRNA translation and its absence in fragile X cells leads to alteration in protein synthesis. In neurons, FMRP is thought to repress specific mRNAs during their transport as silent ribonucleoparticles (mRNPs) from the cell body to the distant synapses which are the sites of local synthesis of neuro-specific proteins. The mechanism by which FMRP sorts out its different mRNAs targets might be tuned by the intervention of different proteins. Using a yeast two-hybrid system, we identified MicroSpherule Protein 58 (MSP58) as a novel FMRP-cellular partner. In cell cultures, we found that MSP58 is predominantly present in the nucleus where it interacts with the nuclear isoform of FMRP. However, in neurons but not in glial cells, MSP58 is also present in the cytoplasmic compartment, as well as in neuritis, where it colocalises with FMRP. Biochemical evidence is given that MSP58 is associated with polyribosomal poly(A)+ mRNPs. We also show that MSP58, similarily to FMRP, is present on polyribosomes prepared from synaptoneurosomes and that it behaves as an RNA-binding protein with a high affinity to the G-quartet structure. We propose that this novel cellular partner for FMRP escorts FMRP-containing mRNP from the nucleus and nucleolus to the somato-dendritic compartment where it might participate in neuronal translation regulation.
Received February 14, 2006
Revised March 19, 2006
Accepted March 19, 2006
Article
The Nuclear MicroSpherule Protein 58 is a novel RNA-binding Protein that Interacts with Fragile X Mental Retardation Protein in Polyribosomal mRNPs from neurons
Laetitia Davidovic 1,
Elias Bechara 2,
Maud Gravel 1,
Xavier H. Jaglin 1,
Sandra Tremblay 1,
Attila Sik 3,
Barbara Bardoni 2,
and
Edouard W. Khandjian 4 *
2 UMR 6543, Faculté de Médecine, Université de Nice, Nice 06107, France
3 Département de Psychiatrie, Faculté de médecine, Centre de recherche Université Laval Robert-Giffard, Québec G1J 2G3, Canada
4 Unité de Recherche en Génétique Humaine et Moléculaire, Centre de recherche Hôpital Saint-François d'Assise, 10 rue de l'Espinay, le CHUQ, Québec G1L 3L5, PQ, Canada; Département de biologie médicale, Faculté de médecine, Université Laval, Québec, Canada
Edouard W. Khandjian, E-mail: edward.khandjian{at}crsfa.ulaval.ca
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