{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:55:13Z","timestamp":1791276913250,"version":"4.1.0"},"reference-count":44,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10,12]]},"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of motor neurons in patients with null mutations in the SMN1 gene. The almost identical SMN2 gene is unable to compensate for this deficiency because of the skipping of exon 7 during pre\u2013messenger RNA (mRNA) processing. Although several splicing factors can modulate SMN2 splicing in vitro, the physiological regulators of this disease-causing event are unknown. We found that knockout of the splicing factor SAM68 partially rescued body weight and viability of SMA\u03947 mice. Ablation of SAM68 function promoted SMN2 splicing and expression in SMA\u03947 mice, correlating with amelioration of SMA-related defects in motor neurons and skeletal muscles. Mechanistically, SAM68 binds to SMN2 pre-mRNA, favoring recruitment of the splicing repressor hnRNP A1 and interfering with that of U2AF65 at the 3\u2032 splice site of exon 7. These findings identify SAM68 as the first physiological regulator of SMN2 splicing in an SMA mouse model.<\/jats:p>","DOI":"10.1083\/jcb.201502059","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T02:17:52Z","timestamp":1444097872000},"page":"77-90","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["SAM68 is a physiological regulator of <i>SMN2<\/i> splicing in spinal muscular atrophy"],"prefix":"10.1083","volume":"211","author":[{"given":"Vittoria","family":"Pagliarini","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy 1"},{"name":"Laboratory of Neuroembryology, Fondazione Santa Lucia, 00143 Rome, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pelosi","sequence":"additional","affiliation":[{"name":"Institute Pasteur Cenci-Bolognetti Foundation, DAHFMO-Unit of Histology and Medical Embryology, IIM, University of Rome La Sapienza, 00161 Rome, Italy 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Blaire","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy 1"},{"name":"Laboratory of Neuroembryology, Fondazione Santa Lucia, 00143 Rome, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Nobili","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Fondazione Santa Lucia, 00143 Rome, Italy 3"},{"name":"Medical School University Campus Bio-Medico, 00128 Rome, Italy 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Institute Pasteur Cenci-Bolognetti Foundation, DAHFMO-Unit of Histology and Medical Embryology, IIM, University of Rome La Sapienza, 00161 Rome, Italy 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"D\u2019Amelio","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Fondazione Santa Lucia, 00143 Rome, Italy 3"},{"name":"Medical School University Campus Bio-Medico, 00128 Rome, Italy 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Musar\u00f2","sequence":"additional","affiliation":[{"name":"Institute Pasteur Cenci-Bolognetti Foundation, DAHFMO-Unit of Histology and Medical Embryology, IIM, University of Rome La Sapienza, 00161 Rome, Italy 4"},{"name":"Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, 00161 Rome, Italy 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sette","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy 1"},{"name":"Laboratory of Neuroembryology, Fondazione Santa Lucia, 00143 Rome, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,10,5]]},"reference":[{"key":"2023072309264916500_bib1","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1002\/ana.23995","article-title":"Spinal muscular atrophy: Development and implementation of potential treatments","volume":"74","author":"Arnold","year":"2013","journal-title":"Ann. 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