The nuclear transcription factor RARα associates with neuronal RNA granules and suppresses translation

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 alpha and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate receptor subunit GluR1. Hippocampal neurons express RAR alpha in dendrites, and knocking down RAR alpha 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 alpha partners with many RNA-binding proteins and translation factors conveyed in dendritic RNA transport granules, including the purine-rich element-binding protein, Pur alpha. The interaction of RAR alpha with Pur alpha, 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 alpha in dendritic RNA granules with Pur alpha and FMRP (the fragile x mental retardation protein). Hippocampal RAR alpha also associates with mRNA, e. g. encoding GluR1 and calcium calmodulin-dependent protein kinase II alpha. Consistent with a granule function of conveying translationally silenced mRNA, RAR alpha 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 alpha also regulates translation.