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Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20303-8. doi: 10.1073/pnas.0807740105. Epub 2008 Dec 10.

Retinoic acid-gated sequence-specific translational control by RARalpha.

Author information

1
Department of Molecular, University of California, Berkeley, CA 94720-3200, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2009 May 5;106(18):7679.

Abstract

Retinoic acid (RA) plays important roles in development by modulating gene transcription through nuclear receptor activation. Increasing evidence supports a role for RA and RA receptors (RARs) in synaptic plasticity in the brain. We have recently reported that RA mediates a type of homeostatic synaptic plasticity through activation of dendritic protein synthesis, a process that requires dendritically localized RARalpha and is independent of transcriptional regulation. The molecular basis of this translational regulation by RA/RARalpha signaling, however, is unknown. Here we show that RARalpha is actively exported from the nucleus. Cytoplasmic RARalpha acts as an RNA-binding protein that associates with a subset of mRNAs, including dendritically localized glutamate receptor 1 (GluR1) mRNA. This binding is mediated by the RARalpha carboxyl terminal F-domain and specific sequence motifs in the 5'UTR of the GluR1 mRNA. Moreover, RARalpha association with the GluR1 mRNA directly underlies the translational control of GluR1 by RA: RARalpha represses GluR1 translation, while RA binding to RARalpha reduces its association with the GluR1 mRNA and relieves translational repression. Taken together, our results demonstrate a ligand-gated translational regulation mechanism mediated by a non-genomic function of RA/RARalpha signaling.

PMID:
19073915
PMCID:
PMC2629326
DOI:
10.1073/pnas.0807740105
[Indexed for MEDLINE]
Free PMC Article

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