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FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons

The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identif...

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Autores principales: Errichelli, Lorenzo, Dini Modigliani, Stefano, Laneve, Pietro, Colantoni, Alessio, Legnini, Ivano, Capauto, Davide, Rosa, Alessandro, De Santis, Riccardo, Scarfò, Rebecca, Peruzzi, Giovanna, Lu, Lei, Caffarelli, Elisa, Shneider, Neil A., Morlando, Mariangela, Bozzoni, Irene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379105/
https://www.ncbi.nlm.nih.gov/pubmed/28358055
http://dx.doi.org/10.1038/ncomms14741
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author Errichelli, Lorenzo
Dini Modigliani, Stefano
Laneve, Pietro
Colantoni, Alessio
Legnini, Ivano
Capauto, Davide
Rosa, Alessandro
De Santis, Riccardo
Scarfò, Rebecca
Peruzzi, Giovanna
Lu, Lei
Caffarelli, Elisa
Shneider, Neil A.
Morlando, Mariangela
Bozzoni, Irene
author_facet Errichelli, Lorenzo
Dini Modigliani, Stefano
Laneve, Pietro
Colantoni, Alessio
Legnini, Ivano
Capauto, Davide
Rosa, Alessandro
De Santis, Riccardo
Scarfò, Rebecca
Peruzzi, Giovanna
Lu, Lei
Caffarelli, Elisa
Shneider, Neil A.
Morlando, Mariangela
Bozzoni, Irene
author_sort Errichelli, Lorenzo
collection PubMed
description The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUS(P525L) mutation associated with ALS.
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spelling pubmed-53791052017-04-11 FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons Errichelli, Lorenzo Dini Modigliani, Stefano Laneve, Pietro Colantoni, Alessio Legnini, Ivano Capauto, Davide Rosa, Alessandro De Santis, Riccardo Scarfò, Rebecca Peruzzi, Giovanna Lu, Lei Caffarelli, Elisa Shneider, Neil A. Morlando, Mariangela Bozzoni, Irene Nat Commun Article The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUS(P525L) mutation associated with ALS. Nature Publishing Group 2017-03-30 /pmc/articles/PMC5379105/ /pubmed/28358055 http://dx.doi.org/10.1038/ncomms14741 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Errichelli, Lorenzo
Dini Modigliani, Stefano
Laneve, Pietro
Colantoni, Alessio
Legnini, Ivano
Capauto, Davide
Rosa, Alessandro
De Santis, Riccardo
Scarfò, Rebecca
Peruzzi, Giovanna
Lu, Lei
Caffarelli, Elisa
Shneider, Neil A.
Morlando, Mariangela
Bozzoni, Irene
FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
title FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
title_full FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
title_fullStr FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
title_full_unstemmed FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
title_short FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
title_sort fus affects circular rna expression in murine embryonic stem cell-derived motor neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379105/
https://www.ncbi.nlm.nih.gov/pubmed/28358055
http://dx.doi.org/10.1038/ncomms14741
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