{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:10:31Z","timestamp":1791169831276,"version":"4.1.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,2,27]]},"abstract":"<jats:p>\n                    The neurodegenerative disease spinal muscular atrophy is caused by mutation of the\n                    <jats:italic>survival motor neuron 1<\/jats:italic>\n                    (\n                    <jats:italic>SMN1<\/jats:italic>\n                    ) gene.\n                    <jats:italic>SMN2<\/jats:italic>\n                    is a nearly identical copy of\n                    <jats:italic>SMN1<\/jats:italic>\n                    that is unable to prevent disease, because most\n                    <jats:italic>SMN2<\/jats:italic>\n                    transcripts lack exon 7 and thus produce a nonfunctional protein. A key cause of inefficient\n                    <jats:italic>SMN2<\/jats:italic>\n                    exon 7 splicing is a single nucleotide difference between\n                    <jats:italic>SMN1<\/jats:italic>\n                    and\n                    <jats:italic>SMN2<\/jats:italic>\n                    within exon 7. We previously provided evidence that this base change suppresses exon 7 splicing by creating an inhibitory element, a heterogeneous nuclear ribonucleoprotein (hnRNP) A1-dependent exonic splicing silencer. We now find that another rare nucleotide difference between\n                    <jats:italic>SMN1<\/jats:italic>\n                    and\n                    <jats:italic>SMN2<\/jats:italic>\n                    , in intron 7, potentially creates a second\n                    <jats:italic>SMN2<\/jats:italic>\n                    -specific hnRNP A1 binding site. Remarkably, this single base change does indeed create a high-affinity hnRNP A1 binding site, and base substitutions that disrupt it restore exon 7 inclusion\n                    <jats:italic>in vivo<\/jats:italic>\n                    and prevent hnRNP A1 binding\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We propose that interactions between hnRNP A1 molecules bound to the exonic and intronic sites cooperate to exclude exon 7 and discuss the significance of this exclusion with respect to\n                    <jats:italic>SMN<\/jats:italic>\n                    expression and splicing control more generally.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0700343104","type":"journal-article","created":{"date-parts":[[2007,2,16]],"date-time":"2007-02-16T20:57:20Z","timestamp":1171659440000},"page":"3426-3431","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["An intronic element contributes to splicing repression in spinal muscular atrophy"],"prefix":"10.1073","volume":"104","author":[{"given":"Tsuyoshi","family":"Kashima","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 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