RGD Reference Report - Retinoic acid-gated sequence-specific translational control by RARalpha. - Rat Genome Database

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

Authors: Poon, MM  Chen, L 
Citation: Poon MM and Chen L, Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20303-8. Epub 2008 Dec 10.
RGD ID: 2314253
Pubmed: PMID:19073915   (View Abstract at PubMed)
PMCID: PMC2629326   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0807740105   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RaraRatnegative regulation of translation  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RaraRatdendrite  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RaraRatmRNA 5'-UTR binding  IDA  RGD 
RaraRatmRNA regulatory element binding translation repressor activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rara  (retinoic acid receptor, alpha)


Additional Information