Dynamic Control of Dendritic mRNA Expression by CNOT7 Regulates Synaptic Efficacy and Higher Cognitive Function

• Published in: Cell reports (Cambridge) Vol. 20; no. 3; pp. 683 - 696
• Main Authors: McFleder, Rhonda L., Mansur, Fernanda, Richter, Joel D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-07-2017; Elsevier
• Subjects: Animals; CNOT7; Cognition - physiology; deadenylation; Dendrites - genetics; Dendrites - metabolism; Hippocampus - metabolism; Learning - physiology; Male; Mice; polyadenylation; Proteins - genetics; Proteins - metabolism; RNA transport; RNA, Messenger - genetics; RNA, Messenger - metabolism; Synapses - genetics; Synapses - metabolism; translation; polyadenylation; translation; CNOT7; RNA transport; deadenylation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.06.078

Translation of mRNAs in dendrites mediates synaptic plasticity, the probable cellular basis of learning and memory. Coordination of translational inhibitory and stimulatory mechanisms, as well as dendritic transport of mRNA, is necessary to ensure proper control of this local translation. Here, we find that the deadenylase CNOT7 dynamically regulates dendritic mRNA translation and transport, as well as synaptic plasticity and higher cognitive function. In cultured hippocampal neurons, synaptic stimulation induces a rapid decrease in CNOT7, which, in the short-term, results in poly(A) tail lengthening of target mRNAs. However, at later times following stimulation, decreased poly(A) and dendritic localization of mRNA take place, similar to what is observed when CNOT7 is depleted over several days. In mice, CNOT7 is essential for hippocampal-dependent learning and memory. This study identifies CNOT7 as an important regulator of RNA transport and translation in dendrites, as well as higher cognitive function.
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•CNOT7 regulates dendritic mRNA transport and local translation•CNOT7 regulates synaptic plasticity in cultured neurons•Dendritic CNOT7 is destroyed during synaptic stimulation•Depletion of CNOT7 from the hippocampus impairs cognitive function
McFleder et al. find that CNOT7, the major deadenylase in eukaryotes, has a specialized role in neurons. CNOT7 regulates the dendritic localization and translation of specific mRNAs and mediates synaptic plasticity and learning and memory in mice.