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J. Biol. Chem., Vol. 280, Issue 39, 33403-33410, September 30, 2005

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Fragile X Mental Retardation Protein (FMRP) Binds Specifically to the Brain Cytoplasmic RNAs BC1/BC200 via a Novel RNA-binding Motif^*

Francesca Zalfa1, Salvatore Adinolfi, Ilaria Napoli, Eva Kühn-Hölsken¶, Henning Urlaub¶, Tilmann Achsel||, Annalisa Pastore, and Claudia Bagni||2

From the Dipartimento di Biologia, Università "Tor Vergata," 00133 Rome, Italy, the Molecular Structure Division, National Institute for Medical Research, London NW7 1AA, United Kingdom, the ^||Istituto di Neuroscienze Sperimentali, Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, 00179 Rome, Italy, and the ^¶Department of Cellular Biochemistry, Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany

Fragile X mental retardation protein (FMRP), the protein responsible for the fragile X syndrome, is an RNA-binding protein involved in localization and translation of neuronal mRNAs. One of the RNAs known to interact with FMRP is the dendritic non-translatable brain cytoplasmic RNA 1 BC1 RNA that works as an adaptor molecule linking FMRP and some of its regulated mRNAs. Here, we showed that the N terminus of FMRP binds strongly and specifically to BC1 and to its potential human analog BC200. This region does not contain a motif known to specifically recognize RNA and thus constitutes a new RNA-binding motif. We further demonstrated that FMRP recognition involves the 5' stem loop of BC1 and that this is the region that exhibits complementarity to FMRP target mRNAs, raising the possibility that FMRP plays a direct role in BC1/mRNA annealing.

Received for publication, April 19, 2005 , and in revised form, June 8, 2005.

^* This work was supported by grants from the Human Frontier Science Program (Grant RGP0052/2001-B), Telethon-Italy (Grant GGP02357), and the MIUR-FIRB (Ministero dell'Istruzione, dell'Università e della Ricerca-Fondi di Investimento per la Ricerca de Base). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a fellowship from the Associazione Italiana Sindrome X Fragile.

² To whom correspondence should be addressed: Università di Roma "Tor Vergata," Dipartimento di Biologia, Via della Ricerca Scientifica 1, 00133 Rome, Italy. Tel.: 39-06-72594223; Fax: 39-06-2023500; E-mail: claudia.bagni{at}uniroma2.it.

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