{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:08:05Z","timestamp":1790665685349,"version":"4.1.0"},"reference-count":119,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Cure SMA Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spinal muscular atrophy (SMA) is characterized by the loss of alpha motor neurons in the spinal cord and a progressive muscle weakness and atrophy. SMA is caused by loss-of-function mutations and\/or deletions in the survival of motor neuron (SMN) gene. The role of SMN in motor neurons has been extensively studied, but its function and the consequences of its loss in muscle have also emerged as a key aspect of SMA pathology. In this study, we explore the molecular mechanisms involved in muscle defects in SMA. First, we show in C2C12 myoblasts, that arginine methylation by CARM1 controls myogenic differentiation. More specifically, the methylation of HuR on K217 regulates HuR levels and subcellular localization during myogenic differentiation, and the formation of myotubes. Furthermore, we demonstrate that SMN and HuR interact in C2C12 myoblasts. Interestingly, the SMA-causing E134K point mutation within the SMN Tudor domain, and CARM1 depletion, modulate the SMN\u2013HuR interaction. In addition, using the Smn2B\/\u2212 mouse model, we report that CARM1 levels are markedly increased in SMA muscles and that HuR fails to properly respond to muscle denervation, thereby affecting the regulation of its mRNA targets. Altogether, our results show a novel CARM1\u2013HuR axis in the regulation of muscle differentiation and plasticity as well as in the aberrant regulation of this axis caused by the absence of SMN in SMA muscle. With the recent developments of therapeutics targeting motor neurons, this study further indicates the need for more global therapeutic approaches for SMA.<\/jats:p>","DOI":"10.1093\/hmg\/ddab333","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T20:11:18Z","timestamp":1636747878000},"page":"1453-1470","source":"Crossref","is-referenced-by-count":8,"title":["A novel CARM1\u2013HuR axis involved in muscle differentiation and plasticity misregulated in spinal muscular atrophy"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-7372","authenticated-orcid":false,"given":"Aymeric","family":"Ravel-Chapuis","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Haghandish","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasibeh","family":"Daneshvar","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard J","family":"Jasmin","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"C\u00f4t\u00e9","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"2022050521122262800_ref1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-017-0671-8","article-title":"Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review","volume":"12","author":"Verhaart","year":"2017","journal-title":"Orphanet J. 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