{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:34:05Z","timestamp":1791617645829,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG18790"],"award-info":[{"award-number":["IG18790"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"publisher","award":["GGP14095"],"award-info":[{"award-number":["GGP14095"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["PRIN 2018"],"award-info":[{"award-number":["PRIN 2018"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministry of Health, Italy","doi-asserted-by":"publisher","award":["GR-2018-12365706"],"award-info":[{"award-number":["GR-2018-12365706"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Spinal Muscular Atrophy (SMA) gene SMN was recently duplicated (SMN1 and SMN2) in higher primates. Furthermore, invasion of the locus by repetitive elements almost doubled its size with respect to mouse Smn, in spite of an almost identical protein-coding sequence. Herein, we found that SMN ranks among the human genes with highest density of Alus, which are evolutionary conserved in primates and often occur in inverted orientation. Inverted repeat Alus (IRAlus) negatively regulate splicing of long introns within SMN, while promoting widespread alternative circular RNA (circRNA) biogenesis. Bioinformatics analyses revealed the presence of ultra-conserved Sam68 binding sites in SMN IRAlus. Cross-link-immunoprecipitation (CLIP), mutagenesis and silencing experiments showed that Sam68 binds in proximity of intronic Alus in the SMN pre-mRNA, thus favouring circRNA biogenesis in vitro and in vivo. These findings highlight a novel layer of regulation in SMN expression, uncover the crucial impact exerted by IRAlus and reveal a role for Sam68 in SMN circRNA biogenesis.<\/jats:p>","DOI":"10.1093\/nar\/gkz1117","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T15:10:38Z","timestamp":1574435438000},"page":"633-645","source":"Crossref","is-referenced-by-count":69,"title":["Sam68 binds Alu-rich introns in SMN and promotes pre-mRNA circularization"],"prefix":"10.1093","volume":"48","author":[{"given":"Vittoria","family":"Pagliarini","sequence":"first","affiliation":[{"name":"Institute of Human Anatomy and Cell Biology, Catholic University of the Sacred Heart, Rome\u00a000168, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Jolly","sequence":"additional","affiliation":[{"name":"GenoSplice Technology, iPEPS-ICM, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, Paris\u00a075013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-8345","authenticated-orcid":false,"given":"Pamela","family":"Bielli","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroembryology, IRCCS Fondazione Santa Lucia, Rome\u00a000143, Italy"},{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome\u00a000133, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Di\u00a0Rosa","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroembryology, IRCCS Fondazione Santa Lucia, Rome\u00a000143, Italy"},{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome\u00a000133, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"De\u00a0la\u00a0Grange","sequence":"additional","affiliation":[{"name":"GenoSplice Technology, iPEPS-ICM, H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, Paris\u00a075013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sette","sequence":"additional","affiliation":[{"name":"Institute of Human Anatomy and Cell Biology, Catholic University of the Sacred Heart, Rome\u00a000168, Italy"},{"name":"Laboratory of Neuroembryology, IRCCS Fondazione Santa Lucia, Rome\u00a000143, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"2020011102345805400_B1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nature02919","article-title":"The DNA sequence and comparative analysis of human chromosome 5","volume":"431","author":"Schmutz","year":"2004","journal-title":"Nature"},{"key":"2020011102345805400_B2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"2020011102345805400_B3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/ahg.12031","article-title":"Spinal muscular atrophy: from gene discovery to clinical trials","volume":"77","author":"Nurputra","year":"2013","journal-title":"Ann. 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