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An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons

Andreassi, C; Zimmermann, C; Mitter, R; Fusco, S; Devita, S; Saiardi, A; Riccio, A; (2010) An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons. NAT NEUROSCI , 13 (3) 291 - U6. 10.1038/nn.2486.

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Abstract

mRNA localization is an evolutionary conserved mechanism that underlies the establishment of cellular polarity and specialized cell functions. To identify mRNAs localized in subcellular compartments of developing neurons, we took an original approach that combines compartmentalized cultures of rat sympathetic neurons and sequential analysis of gene expression (SAGE). Unexpectedly, the most abundant transcript in axons was mRNA for myo-inositol monophosphatase-1 (Impa1), a key enzyme that regulates the inositol cycle and the main target of lithium in neurons. A novel localization element within the 3' untranslated region of Impa1 mRNA specifically targeted Impa1 transcript to sympathetic neuron axons and regulated local IMPA1 translation in response to nerve growth factor (NGF). Selective silencing of IMPA1 synthesis in axons decreased nuclear CREB activation and induced axonal degeneration. These results provide insights into mRNA transport in axons and reveal a new NGF-responsive localization element that directs the targeting and local translation of an axonal transcript.

Type: Article
Title: An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons
DOI: 10.1038/nn.2486
Keywords: LOCAL PROTEIN-SYNTHESIS, GROWTH CONES, INOSITOL POLYPHOSPHATES, TRANSCRIPTION FACTOR, HIPPOCAMPAL-NEURONS, UNIFYING HYPOTHESIS, TRANSLATION, ACTIN, LOCALIZATION, SURVIVAL
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/114906
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