{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:44:08Z","timestamp":1791384248691,"version":"4.3.3"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,8,15]]},"abstract":"<jats:p>\n                    Spinal muscular atrophy (SMA), a common motor neuron disease in humans, results from loss of functional survival motor neuron (\n                    <jats:italic>SMN1<\/jats:italic>\n                    ) alleles. A nearly identical copy of the gene,\n                    <jats:italic>SMN2<\/jats:italic>\n                    , fails to provide protection from SMA because of a single translationally silent nucleotide difference in exon 7. This likely disrupts an exonic splicing enhancer and causes exon 7 skipping, leading to abundant production of a shorter isoform,\n                    <jats:italic>SMN2\u0394<\/jats:italic>\n                    <jats:italic>7<\/jats:italic>\n                    . The truncated transcript encodes a less stable protein with reduced self-oligomerization activity that fails to compensate for the loss of\n                    <jats:italic>SMN1.<\/jats:italic>\n                    This report describes the identification of an\n                    <jats:italic>in vivo<\/jats:italic>\n                    regulator of\n                    <jats:italic>SMN<\/jats:italic>\n                    mRNA processing. Htra2-\u03b21, an SR-like splicing factor and ortholog of\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    transformer-2, promoted the inclusion of\n                    <jats:italic>SMN<\/jats:italic>\n                    exon 7, which would stimulate full-length\n                    <jats:italic>SMN<\/jats:italic>\n                    2 expression. Htra2-\u03b21 specifically functioned through and bound an AG-rich exonic splicing enhancer in\n                    <jats:italic>SMN<\/jats:italic>\n                    exon 7. This effect is not species-specific as expression of Htra2-\u03b21 in human or mouse cells carrying an\n                    <jats:italic>SMN2<\/jats:italic>\n                    minigene dramatically increased production of full-length\n                    <jats:italic>SMN2.<\/jats:italic>\n                    This demonstrates that\n                    <jats:italic>SMN2<\/jats:italic>\n                    mRNA processing can be modulated\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Because all SMA patients retain at least one\n                    <jats:italic>SMN2<\/jats:italic>\n                    copy, these results show that an\n                    <jats:italic>in vivo<\/jats:italic>\n                    modulation of\n                    <jats:italic>SMN<\/jats:italic>\n                    RNA processing could serve as a therapeutic strategy to prevent SMA.\n                  <\/jats:p>","DOI":"10.1073\/pnas.160181697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"9618-9623","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":269,"title":["<i>Htra2-\u03b2<\/i>\n                    <i>1<\/i>\n                    stimulates an exonic splicing enhancer and can restore full-length\n                    <i>SMN<\/i>\n                    expression to\n                    <i>survival motor neuron<\/i>\n                    2 (\n                    <i>SMN2<\/i>\n                    )"],"prefix":"10.1073","volume":"97","author":[{"given":"Yvonne","family":"Hofmann","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53111 Bonn, Germany; Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111; and Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian L.","family":"Lorson","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53111 Bonn, Germany; Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111; and Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Stamm","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53111 Bonn, Germany; Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111; and Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot J.","family":"Androphy","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53111 Bonn, Germany; Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111; and Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunhilde","family":"Wirth","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, 53111 Bonn, Germany; Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111; and Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,8,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)90847-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(06)80015-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-265"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1205"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-63"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11167"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6307"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.259"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.65.070196.002055"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80050-7"},{"key":"e_1_3_3_13_2","first-page":"663","volume":"1","author":"Fu 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