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Regulation of NGF Signaling by an Axonal Untranslated mRNA

Crerar, H; Scott-Solomon, E; Bodkin-Clarke, C; Andreassi, C; Hazbon, M; Logie, E; Cano-Jaimez, M; ... Riccio, A; + view all (2019) Regulation of NGF Signaling by an Axonal Untranslated mRNA. Neuron 10.1016/j.neuron.2019.02.011. (In press). Green open access

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Abstract

Neurons are extraordinarily large and highly polarized cells that require rapid and efficient communication between cell bodies and axons over long distances. In peripheral neurons, transcripts are transported along axons to growth cones, where they are rapidly translated in response to extrinsic signals. While studying Tp53inp2, a transcript highly expressed and enriched in sympathetic neuron axons, we unexpectedly discovered that Tp53inp2 is not translated. Instead, the transcript supports axon growth in a coding-independent manner. Increasing evidence indicates that mRNAs may function independently of their coding capacity; for example, acting as a scaffold for functionally related proteins. The Tp53inp2 transcript interacts with the nerve growth factor (NGF) receptor TrkA, regulating TrkA endocytosis and signaling. Deletion of Tp53inp2 inhibits axon growth in vivo, and the defects are rescued by a non-translatable form of the transcript. Tp53inp2 is an atypical mRNA that regulates axon growth by enhancing NGF-TrkA signaling in a translation-independent manner.

Type: Article
Title: Regulation of NGF Signaling by an Axonal Untranslated mRNA
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuron.2019.02.011
Publisher version: http://doi.org/10.1016/j.neuron.2019.02.011
Language: English
Additional information: Copyright © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: 3′untranslated region, RNA localization, axons, neuronal development, neurotrophin-signaling, sympathetic neurons
UCL classification: UCL
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10070840
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