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Updated: Jun 27, 2026
09:07
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Retinoic acid-gated sequence-specific translational control by RARalpha
1Department of Molecular, University of California, Berkeley, CA 94720-3200, USA.
Summary
Retinoic acid (RA) controls brain cell communication by regulating protein synthesis. RA signaling directly impacts synaptic plasticity by controlling the translation of specific mRNAs via its receptor, RARalpha.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Retinoic acid (RA) is crucial for development and gene transcription via nuclear receptors.
- RA and its receptors (RARs) are increasingly linked to synaptic plasticity in the brain.
- Previous work showed RA influences synaptic plasticity through dendritic protein synthesis, independent of transcription.
Purpose of the Study:
- To elucidate the molecular mechanisms of retinoic acid's translational regulation of synaptic plasticity.
- To investigate the role of RARalpha in controlling mRNA translation in neurons.
Main Methods:
- Investigated nuclear export of RARalpha.
- Identified RARalpha as an RNA-binding protein associated with specific mRNAs.
- Mapped the binding interaction between RARalpha and glutamate receptor 1 (GluR1) mRNA.
- Assessed the effect of RA on RARalpha-mRNA binding and GluR1 translation.
Main Results:
- RARalpha is actively exported from the nucleus to the cytoplasm.
- Cytoplasmic RARalpha binds to specific mRNAs, including GluR1 mRNA, via its F-domain and mRNA's 5'UTR.
- RARalpha binding represses GluR1 translation.
- RA binding to RARalpha reduces its association with GluR1 mRNA, relieving translational repression.
Conclusions:
- Demonstrated a novel ligand-gated translational regulation mechanism for RA signaling.
- Revealed a non-genomic function of RA/RARalpha in controlling synaptic plasticity via mRNA translation.
- Highlighted RARalpha's role as a cytoplasmic RNA-binding protein regulating neuronal function.
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