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J. Biol. Chem., Vol. 283, Issue 30, 20841-20847, July 25, 2008

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The Nuclear Transcription Factor RAR Associates with Neuronal RNA Granules and Suppresses Translation^*

Na Chen, Bruce Onisko, and Joseph L. Napoli¹

From the Department of Nutritional Science and Toxicology, University of California, Berkeley, California 94720 and the Western Regional Research Center, United States Department of Agriculture, Albany, California 94710

All-trans-retinoic acid stimulates dendritic growth in hippocampal neurons within minutes by activating mitogen-activated protein kinase and mTOR and increasing dendritic translation of calcium calmodulin-dependent protein kinase II and the -amino-3-hydroxyl-5-methyl-4-isoxazole propionate receptor subunit GluR1. Hippocampal neurons express RAR in dendrites, and knocking down RAR prevents all-trans-retinoic acid effects on dendritic growth. Here we show, by liquid chromatography/mass spectrometry analysis of immunoaffinity isolates of hippocampal neurons, that RAR partners with many RNA-binding proteins and translation factors conveyed in dendritic RNA transport granules, including the purine-rich element-binding protein, Pur . The interaction of RAR with Pur , an RNA-binding protein required for dendritic RNA transport, and other RNA-binding proteins was confirmed by tandem affinity purification. Confocal microscopy confirmed localization of neuronal RAR in dendritic RNA granules with Pur and FMRP (the fragile x mental retardation protein). Hippocampal RAR also associates with mRNA, e.g. encoding GluR1 and calcium calmodulin-dependent protein kinase II . Consistent with a granule function of conveying translationally silenced mRNA, RAR inhibits translation initiation, independent of 7-methylguanylate cap or poly(A) tail, and prompts mRNA redistribution to silencing ribonucleoprotein particles. These data afford a mechanism for rapid stimulation of dendritic growth by all-trans-retinoic acid and reveal that the ligand-dependent transcription factor RAR also regulates translation.

Received for publication, March 25, 2008 , and in revised form, May 19, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants DK36870 and AG13566. 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 To whom correspondence should be addressed: 119 Morgan Hall, MC#3104, University of California, Berkeley, CA 94720-3104. Fax: 510-642-0535; E-mail: jna{at}berkeley.edu.

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				M. M. Poon and L. Chen Retinoic acid-gated sequence-specific translational control by RAR{alpha} PNAS, December 23, 2008; 105(51): 20303 - 20308. [Abstract] [Full Text] [PDF]