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Sumoylation regulates the assembly and activity of the SMN complex
SMN is a ubiquitously expressed protein and is essential for life. SMN deficiency causes the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. SMN interacts with itself and other proteins to form a complex that functions in the assembly of ribonu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376998/ https://www.ncbi.nlm.nih.gov/pubmed/34413305 http://dx.doi.org/10.1038/s41467-021-25272-5 |
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author | Riboldi, Giulietta M. Faravelli, Irene Kuwajima, Takaaki Delestrée, Nicolas Dermentzaki, Georgia De Planell-Saguer, Mariangels Rinchetti, Paola Hao, Le Thi Beattie, Christine C. Corti, Stefania Przedborski, Serge Mentis, George Z. Lotti, Francesco |
author_facet | Riboldi, Giulietta M. Faravelli, Irene Kuwajima, Takaaki Delestrée, Nicolas Dermentzaki, Georgia De Planell-Saguer, Mariangels Rinchetti, Paola Hao, Le Thi Beattie, Christine C. Corti, Stefania Przedborski, Serge Mentis, George Z. Lotti, Francesco |
author_sort | Riboldi, Giulietta M. |
collection | PubMed |
description | SMN is a ubiquitously expressed protein and is essential for life. SMN deficiency causes the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. SMN interacts with itself and other proteins to form a complex that functions in the assembly of ribonucleoproteins. SMN is modified by SUMO (Small Ubiquitin-like Modifier), but whether sumoylation is required for the functions of SMN that are relevant to SMA pathogenesis is not known. Here, we show that inactivation of a SUMO-interacting motif (SIM) alters SMN sub-cellular distribution, the integrity of its complex, and its function in small nuclear ribonucleoproteins biogenesis. Expression of a SIM-inactivated mutant of SMN in a mouse model of SMA slightly extends survival rate with limited and transient correction of motor deficits. Remarkably, although SIM-inactivated SMN attenuates motor neuron loss and improves neuromuscular junction synapses, it fails to prevent the loss of sensory-motor synapses. These findings suggest that sumoylation is important for proper assembly and function of the SMN complex and that loss of this post-translational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of SMA mice. |
format | Online Article Text |
id | pubmed-8376998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83769982021-09-22 Sumoylation regulates the assembly and activity of the SMN complex Riboldi, Giulietta M. Faravelli, Irene Kuwajima, Takaaki Delestrée, Nicolas Dermentzaki, Georgia De Planell-Saguer, Mariangels Rinchetti, Paola Hao, Le Thi Beattie, Christine C. Corti, Stefania Przedborski, Serge Mentis, George Z. Lotti, Francesco Nat Commun Article SMN is a ubiquitously expressed protein and is essential for life. SMN deficiency causes the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. SMN interacts with itself and other proteins to form a complex that functions in the assembly of ribonucleoproteins. SMN is modified by SUMO (Small Ubiquitin-like Modifier), but whether sumoylation is required for the functions of SMN that are relevant to SMA pathogenesis is not known. Here, we show that inactivation of a SUMO-interacting motif (SIM) alters SMN sub-cellular distribution, the integrity of its complex, and its function in small nuclear ribonucleoproteins biogenesis. Expression of a SIM-inactivated mutant of SMN in a mouse model of SMA slightly extends survival rate with limited and transient correction of motor deficits. Remarkably, although SIM-inactivated SMN attenuates motor neuron loss and improves neuromuscular junction synapses, it fails to prevent the loss of sensory-motor synapses. These findings suggest that sumoylation is important for proper assembly and function of the SMN complex and that loss of this post-translational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of SMA mice. Nature Publishing Group UK 2021-08-19 /pmc/articles/PMC8376998/ /pubmed/34413305 http://dx.doi.org/10.1038/s41467-021-25272-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Riboldi, Giulietta M. Faravelli, Irene Kuwajima, Takaaki Delestrée, Nicolas Dermentzaki, Georgia De Planell-Saguer, Mariangels Rinchetti, Paola Hao, Le Thi Beattie, Christine C. Corti, Stefania Przedborski, Serge Mentis, George Z. Lotti, Francesco Sumoylation regulates the assembly and activity of the SMN complex |
title | Sumoylation regulates the assembly and activity of the SMN complex |
title_full | Sumoylation regulates the assembly and activity of the SMN complex |
title_fullStr | Sumoylation regulates the assembly and activity of the SMN complex |
title_full_unstemmed | Sumoylation regulates the assembly and activity of the SMN complex |
title_short | Sumoylation regulates the assembly and activity of the SMN complex |
title_sort | sumoylation regulates the assembly and activity of the smn complex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376998/ https://www.ncbi.nlm.nih.gov/pubmed/34413305 http://dx.doi.org/10.1038/s41467-021-25272-5 |
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