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Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity

Andreassi, C; Luisier, R; Crerar, H; Darsinou, M; Blokzijl-Franke, S; Lenn, T; Luscombe, NM; ... Riccio, A; + view all (2021) Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity. Cell Reports , 34 (8) , Article 108778. 10.1016/j.celrep.2021.108778. Green open access

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Abstract

The 3′ untranslated regions (3′ UTRs) of messenger RNAs (mRNAs) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localization and translation. Incorrect processing and delivery of mRNA cause severe developmental defects and have been implicated in many neurological disorders. Here, we use deep sequencing to show that in sympathetic neuron axons, the 3′ UTRs of many transcripts undergo cleavage, generating isoforms that express the coding sequence with a short 3′ UTR and stable 3′ UTR-derived fragments of unknown function. Cleavage of the long 3′ UTR of Inositol Monophosphatase 1 (IMPA1) mediated by a protein complex containing the endonuclease argonaute 2 (Ago2) generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates an additional class of 3′ UTR-derived RNAs.

Type: Article
Title: Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2021.108778
Publisher version: https://doi.org/10.1016/j.celrep.2021.108778
Language: English
Additional information: Copyright © 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: 3’UTR, 3’UTR cleavage, NGF, RNA processing, alternative polyadenylation, axons, local translation, mRNA localization, neuronal development, 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 > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
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/10122886
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