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Mol Cell. 2012 Jul 27;47(2):253-66. doi: 10.1016/j.molcel.2012.05.016. Epub 2012 Jun 21.

Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex.

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1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

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.

PMID:
22727665
PMCID:
PMC3408552
DOI:
10.1016/j.molcel.2012.05.016
[Indexed for MEDLINE]
Free PMC Article

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