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| Content Provider | PubMed Central |
|---|---|
| Author | Poon, Michael M. Chen, Lu |
| 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 RARα and is independent of transcriptional regulation. The molecular basis of this translational regulation by RA/RARα signaling, however, is unknown. Here we show that RARα is actively exported from the nucleus. Cytoplasmic RARα 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 RARα carboxyl terminal F-domain and specific sequence motifs in the 5′UTR of the GluR1 mRNA. Moreover, RARα association with the GluR1 mRNA directly underlies the translational control of GluR1 by RA: RARα represses GluR1 translation, while RA binding to RARα 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/RARα signaling. |
| Related Links | http://dx.doi.org/10.1073/pnas.0807740105 |
| Ending Page | 20308 |
| Page Count | 6 |
| Starting Page | 20303 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 51 |
| Volume Number | 105 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2008-12-23 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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