Nucleic Acids Research Advance Access originally published online on January 9, 2009
Nucleic Acids Research 2009 37(4):1269-1279; doi:10.1093/nar/gkn1058
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Nucleic Acids Research, 2009, Vol. 37, No. 4 1269-1279
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure
1CNRS UMR 6097-Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, 2Université de Nice Sophia-Antipolis, Nice, France, 3Institute of Neurological Sciences National Research Council (CNR), Catania, 4Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, University of Catania, 5Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Troina, Italy and 6Department of Genetic Medicine Women's and Children's Hospital and School of Pediatric and Reproductive Health, University of Adelaide, Adelaide, Australia
*To whom correspondence should be addressed. Tel: +33 4 93957755; Fax: +33 4 93957708; Email: bardoni{at}ipmc.cnrs.fr
Received October 26, 2008. Revised December 14, 2008. Accepted December 17, 2008.
FRAXE is a form of mild to moderate mental retardation due to the silencing of the FMR2 gene. The cellular function of FMR2 protein is presently unknown. By analogy with its homologue AF4, FMR2 was supposed to have a role in transcriptional regulation, but robust evidences supporting this hypothesis are lacking. We observed that FMR2 co-localizes with the splicing factor SC35 in nuclear speckles, the nuclear regions where splicing factors are concentrated, assembled and modified. Similarly to what was reported for splicing factors, blocking splicing or transcription leads to the accumulation of FMR2 in enlarged, rounded speckles. FMR2 is also localized in the nucleolus when splicing is blocked. We show here that FMR2 is able to specifically bind the G-quartet-forming RNA structure with high affinity. Remarkably, in vivo, in the presence of FMR2, the ESE action of the G-quartet situated in mRNA of an alternatively spliced exon of a minigene or of the putative target FMR1 appears reduced. Interestingly, FMR1 is silenced in the fragile X syndrome, another form of mental retardation. All together, our findings strongly suggest that FMR2 is an RNA-binding protein, which might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure.