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Activity-dependent polyadenylation in neurons.

Ling Du1, Joel D Richter

  • 1University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605, USA.

RNA (New York, N.Y.)
|July 27, 2005
PubMed
Summary
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This study identifies novel mRNAs regulated by cytoplasmic polyadenylation element-binding protein (CPEB) in neurons. Activity-dependent polyadenylation of these mRNAs enhances synaptic plasticity and protein synthesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • RNA Biology

Background:

  • Synaptic efficacy is modulated by activity-dependent protein synthesis.
  • Cytoplasmic polyadenylation, regulated by CPEB, controls mRNA translation in neurons.
  • Existing knowledge of CPEB targets in neurons is limited, despite its role in plasticity.

Purpose of the Study:

  • To identify novel mRNA targets of CPEB-mediated cytoplasmic polyadenylation in neurons.
  • To investigate the role of activity-dependent polyadenylation in synaptic plasticity.
  • To link polyadenylation to increased protein synthesis in the synapto-dendritic compartment.

Main Methods:

  • Developed a functional assay using Xenopus oocytes to screen brain-derived mRNAs for polyadenylation.
  • Isolated polyadenylated RNAs via poly(U) agarose binding and thermal elution.

Related Experiment Videos

  • Validated activity-dependent polyadenylation in cultured hippocampal neurons and measured protein levels in stimulated synaptoneurosomes.

    • Main Results:

    • Identified numerous mRNAs undergoing activity-dependent polyadenylation in neurons.
    • Demonstrated that this polyadenylation process correlates with enhanced translation in the synapto-dendritic compartment.
    • Showcased the broader role of CPEB in regulating neuronal mRNA translation.

    Conclusions:

    • Cytoplasmic polyadenylation is a widespread mechanism for activity-dependent mRNA regulation in neurons.
    • This process is crucial for modulating protein synthesis and synaptic plasticity.
    • The findings expand our understanding of post-transcriptional gene regulation in neuronal function.