BDNF-induced local translation of <i>GluA1</i> is regulated by HNRNP A2/B1.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33219033.
- Also identified by DOI 10.1126/sciadv.abd2163 and PMC identifier 7679154.
- Licence recorded as CC BY-NC.
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Abstract
The AMPA receptor subunit GluA1 is essential for induction of synaptic plasticity. While various regulatory mechanisms of AMPA receptor expression have been identified, the underlying mechanisms of GluA1 protein synthesis are not fully understood. In neurons, axonal and dendritic mRNAs have been reported to be translated in a cap-independent manner. However, molecular mechanisms of cap-independent translation of synaptic mRNAs remain largely unknown. Here, we show that <i>GluA1</i> mRNA contains an internal ribosome entry site (IRES) in the 5'UTR. We also demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 interacts with <i>GluA1</i> mRNA and mediates internal initiation of <i>GluA1</i> Brain-derived neurotrophic factor (BDNF) stimulation increases IRES-mediated <i>GluA1</i> translation via up-regulation of HNRNP A2/B1. Moreover, BDNF-induced GluA1 expression and dendritic spine density were significantly decreased in neurons lacking hnRNP A2/B1. Together, our data demonstrate that IRES-mediated translation of <i>GluA1</i> mRNA is a previously unidentified feature of local expression of the AMPA receptor.