1. Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex.
- Author
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Udagawa T, Swanger SA, Takeuchi K, Kim JH, Nalavadi V, Shin J, Lorenz LJ, Zukin RS, Bassell GJ, and Richter JD
- Subjects
- Animals, Dendrites metabolism, Hippocampus metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Nuclear Proteins metabolism, Polyadenylation, Polynucleotide Adenylyltransferase metabolism, RNA-Binding Proteins metabolism, Rats, Rats, Sprague-Dawley, Repressor Proteins metabolism, Ribonucleoproteins metabolism, Transcription Factors metabolism, mRNA Cleavage and Polyadenylation Factors metabolism, Cytoplasm metabolism, Neuronal Plasticity, Protein Biosynthesis, Synaptic Transmission
- Abstract
Translational control of mRNAs in dendrites is essential for certain forms of synaptic plasticity and learning and memory. CPEB is an RNA-binding protein that regulates local translation in dendrites. Here, we identify poly(A) polymerase Gld2, deadenylase PARN, and translation inhibitory factor neuroguidin (Ngd) as components of a dendritic CPEB-associated polyadenylation apparatus. Synaptic stimulation induces phosphorylation of CPEB, PARN expulsion from the ribonucleoprotein complex, and polyadenylation in dendrites. A screen for mRNAs whose polyadenylation is altered by Gld2 depletion identified >100 transcripts including one encoding NR2A, an NMDA receptor subunit. shRNA depletion studies demonstrate that Gld2 promotes and Ngd inhibits dendritic NR2A expression. Finally, shRNA-mediated depletion of Gld2 in vivo attenuates protein synthesis-dependent long-term potentiation (LTP) at hippocampal dentate gyrus synapses; conversely, Ngd depletion enhances LTP. These results identify a pivotal role for polyadenylation and the opposing effects of Gld2 and Ngd in hippocampal synaptic plasticity., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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