Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity
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Catia Andreassi Raphaëlle Luisier Hamish Crerar Marousa Darsinou Sasja Blokzijl-Franke Tchern Lenn Nicholas Luscombe Giovanni Cuda Marco Gaspari Adolfo Saiardi Antonella RiccioAbstract
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.
Journal details
Journal Cell Reports
Volume 34
Issue number 8
Pages 108778
Available online
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Publisher website (DOI) 10.1016/j.celrep.2021.108778
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Europe PubMed Central 33626357
Pubmed 33626357
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