Human Molecular Genetics Advance Access originally published online on October 7, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 23 3087-3096
DOI: 10.1093/hmg/ddg335
© 2003 Oxford University Press
Fragile X Mental Retardation protein determinants required for its association with polyribosomal mRNPs
Unité de Recherche en Génétique Humaine et Moléculaire, Centre de Recherche Hôpital Saint-François d'Assise, Le CHUQ, Québec, (Qc) G1L 3L5 and Département de Biologie Médicale, Faculté de Médecine, Université Laval, Québec, Canada
Received July 17, 2003; Accepted September 29, 2003
Fragile X Mental Retardation protein (FMRP) is an RNA-binding protein that contains multiple domains with apparently differential affinity to mRNA and to the ribonucleotide homopolymer poly(G). Attempts have been made to map the RNA-binding sites along the protein sequence with a view to determining which of the KH1, KH2 and RGG domains are required to recognize and bind to RNA. While these studies have greatly contributed to the delineation of domains that bind homopolymers or mRNA in vitro, little is known concerning their implications in FMRP function(s) in vivo. To address this question, we have prepared a series of FMRP versions, in which each known in vitro functional domain has been individually deleted, leaving the rest of the protein intact. Constructs with deletions in the protein–protein interaction and RNA-binding as well as in the phosphorylation domains were expressed in STEK-KO cells lacking FMRP and their recruitment into polyribosomal mRNPs and their intra-cellular localization were determined. Our results indicate that the KH RNA-binding domains and the Protein–Protein Interacting domain are essential for FMRP to associate with polyribosomal mRNPs, while the RGG box and the phosphorylated domains are dispensable.
* To whom correspondence should be addressed at: URGHM, Centre de Recherche Hôpital St-François d'Assise, 10 rue de l'Espinay, Québec G1L 3L5, PQ, Canada. Tel: +1 4185254402; Fax: +1 4185254195; Email: edward.khandjian{at}crsfa.ulaval.ca
Present address: Department of Biochemistry, McGill University, Montréal, PQ, Canada.
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