<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-00187889</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-19T03:00:30+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a complex interplay between multiple antagonistic splicing elements.</title>
            <author role="aut">
              <persName>
                <forename type="first">A.</forename>
                <surname>Disset</surname>
              </persName>
              <idno type="halauthorid">141780-0</idno>
              <affiliation ref="#struct-425"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">C. F.</forename>
                <surname>Bourgeois</surname>
              </persName>
              <idno type="halauthorid">241815-0</idno>
              <affiliation ref="#struct-1047"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">N.</forename>
                <surname>Benmalek</surname>
              </persName>
              <idno type="halauthorid">141782-0</idno>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">M.</forename>
                <surname>Claustres</surname>
              </persName>
              <email type="md5">b34f55cb7c214a3fad6508fccd4650e7</email>
              <email type="domain">igh.cnrs.fr</email>
              <idno type="idhal" notation="numeric">837247</idno>
              <idno type="halauthorid" notation="string">141783-837247</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-8659-2646</idno>
              <affiliation ref="#struct-425"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">J.</forename>
                <surname>Stevenin</surname>
              </persName>
              <idno type="halauthorid">141784-0</idno>
              <affiliation ref="#struct-1047"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Sylvie</forename>
                <surname>Tuffery-Giraud</surname>
              </persName>
              <email type="md5">686be73725de382d8e50df1ad4b20fa4</email>
              <email type="domain">inserm.fr</email>
              <idno type="idhal" notation="string">sylvie-tuffery-giraud</idno>
              <idno type="idhal" notation="numeric">179259</idno>
              <idno type="halauthorid" notation="string">3651-179259</idno>
              <idno type="ORCID">https://orcid.org/0000-0001-9369-7780</idno>
              <idno type="IDREF">https://www.idref.fr/099102218</idno>
              <affiliation ref="#struct-425"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Jean-Luc</forename>
                <surname>Toussaint</surname>
              </persName>
              <email type="md5">91dd24c0528ad896937d11a0d5fb6f4a</email>
              <email type="domain">igbmc.u-strasbg.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2007-11-15 14:28:23</date>
              <date type="whenModified">2025-11-21 14:45:42</date>
              <date type="whenReleased">2007-11-15 14:28:23</date>
              <date type="whenProduced">2006-03-15</date>
              <ref type="externalLink" target="https://academic.oup.com/hmg/article-pdf/15/6/999/1564539/ddl015.pdf"/>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="120670">
                <persName>
                  <forename>Jean-Luc</forename>
                  <surname>Toussaint</surname>
                </persName>
                <email type="md5">91dd24c0528ad896937d11a0d5fb6f4a</email>
                <email type="domain">igbmc.u-strasbg.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-00187889</idno>
            <idno type="halUri">https://hal.science/hal-00187889</idno>
            <idno type="halBibtex">disset:hal-00187889</idno>
            <idno type="halRefHtml">&lt;i&gt;Human Molecular Genetics&lt;/i&gt;, 2006, 15 (6), pp.999-1013. &lt;a target="_blank" href="https://dx.doi.org/10.1093/hmg/ddl015"&gt;&amp;#x27E8;10.1093/hmg/ddl015&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Human Molecular Genetics, 2006, 15 (6), pp.999-1013. &amp;#x27E8;10.1093/hmg/ddl015&amp;#x27E9;</idno>
            <availability status="restricted"/>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="UNIV-STRASBG1">Université Louis Pasteur - Strasbourg I</idno>
            <idno type="stamp" n="IGBMC" corresp="INSERM">Institut Génétique de Biologie Moléculaire et Cellulaire</idno>
            <idno type="stamp" n="IGH" corresp="UNIV-MONTPELLIER">Institut de génétique humaine</idno>
            <idno type="stamp" n="UNIV-STRASBG">Université de Strasbourg</idno>
            <idno type="stamp" n="BS">Biologie-Santé</idno>
            <idno type="stamp" n="UNIV-MONTPELLIER">Université de Montpellier</idno>
            <idno type="stamp" n="SITE-ALSACE">Archive ouverte du site Alsace</idno>
            <idno type="stamp" n="UM-2015-2021" corresp="UNIV-MONTPELLIER">Université de Montpellier (2015-2021)</idno>
            <idno type="stamp" n="UNIVOAK">UNIVOAK</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a complex interplay between multiple antagonistic splicing elements.</title>
                <author role="aut">
                  <persName>
                    <forename type="first">A.</forename>
                    <surname>Disset</surname>
                  </persName>
                  <idno type="halauthorid">141780-0</idno>
                  <affiliation ref="#struct-425"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">C. F.</forename>
                    <surname>Bourgeois</surname>
                  </persName>
                  <idno type="halauthorid">241815-0</idno>
                  <affiliation ref="#struct-1047"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">N.</forename>
                    <surname>Benmalek</surname>
                  </persName>
                  <idno type="halauthorid">141782-0</idno>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">M.</forename>
                    <surname>Claustres</surname>
                  </persName>
                  <email type="md5">b34f55cb7c214a3fad6508fccd4650e7</email>
                  <email type="domain">igh.cnrs.fr</email>
                  <idno type="idhal" notation="numeric">837247</idno>
                  <idno type="halauthorid" notation="string">141783-837247</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-8659-2646</idno>
                  <affiliation ref="#struct-425"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">J.</forename>
                    <surname>Stevenin</surname>
                  </persName>
                  <idno type="halauthorid">141784-0</idno>
                  <affiliation ref="#struct-1047"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Sylvie</forename>
                    <surname>Tuffery-Giraud</surname>
                  </persName>
                  <email type="md5">686be73725de382d8e50df1ad4b20fa4</email>
                  <email type="domain">inserm.fr</email>
                  <idno type="idhal" notation="string">sylvie-tuffery-giraud</idno>
                  <idno type="idhal" notation="numeric">179259</idno>
                  <idno type="halauthorid" notation="string">3651-179259</idno>
                  <idno type="ORCID">https://orcid.org/0000-0001-9369-7780</idno>
                  <idno type="IDREF">https://www.idref.fr/099102218</idno>
                  <affiliation ref="#struct-425"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">13958</idno>
                <idno type="issn">0964-6906</idno>
                <idno type="eissn">1460-2083</idno>
                <title level="j">Human Molecular Genetics</title>
                <imprint>
                  <publisher>Oxford University Press (OUP)</publisher>
                  <biblScope unit="volume">15</biblScope>
                  <biblScope unit="issue">6</biblScope>
                  <biblScope unit="pp">999-1013</biblScope>
                  <date type="datePub">2006-03-15</date>
                  <date type="dateEpub">2006-02-06</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1093/hmg/ddl015</idno>
              <idno type="pubmed">16461336</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <classCode scheme="mesh">Amino Acid Motifs</classCode>
              <classCode scheme="mesh">Base Sequence</classCode>
              <classCode scheme="mesh">Molecular Sequence Data</classCode>
              <classCode scheme="mesh">Phenotype</classCode>
              <classCode scheme="mesh">Protein Binding</classCode>
              <classCode scheme="mesh">RNA Precursors</classCode>
              <classCode scheme="mesh">RNA Splicing</classCode>
              <classCode scheme="mesh">Repressor Proteins</classCode>
              <classCode scheme="mesh">Sequence Deletion</classCode>
              <classCode scheme="mesh">Codon, Nonsense</classCode>
              <classCode scheme="mesh">Down-Regulation</classCode>
              <classCode scheme="mesh">Dystrophin</classCode>
              <classCode scheme="mesh">Exons</classCode>
              <classCode scheme="mesh">Gene Expression Regulation</classCode>
              <classCode scheme="mesh">Hela Cells</classCode>
              <classCode scheme="mesh">Heterogeneous-Nuclear Ribonucleoprotein Group A-B</classCode>
              <classCode scheme="mesh">Humans</classCode>
              <classCode scheme="halDomain" n="sdv.bbm.bm">Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>A nonsense mutation c.4250T&gt;A (p.Leu1417X) in the dystrophin gene of a patient with an intermediate phenotype of muscular dystrophy induces partial in-frame skipping of exon 31. On the basis of UV cross-linking assays and pull-down analysis, we present evidence that the skipping of this exon is because of the creation of an exonic splicing silencer, which acts as a highly specific binding site (UAGACA) for a known repressor protein, hnRNP A1. Recombinant hnRNP A1 represses exon inclusion both in vitro and in vivo upon transient transfection of C2C12 cells with Duchenne muscular dystrophy (DMD) minigenes carrying the c.4250T&gt;A mutation. Furthermore, we identified a downstream splicing enhancer in the central region of exon 31. This region functions as a Tra2beta-dependent exonic splicing enhancer (ESE) in vitro when inserted into a heterologous splicing reporter, and deletion of the ESE showed that incorporation of exon 31 depends on the Tra2beta-dependent enhancer both in the wild-type and mutant context. We conclude that dystrophin exon 31 contains juxtaposed sequence motifs that collaborate to regulate exon usage. This is the first elucidation of the molecular mechanism leading to exon skipping in the dystrophin gene and allowing the occurrence of a milder phenotype than the expected DMD phenotype. The knowledge of which cis-acting sequence within an exon is important for its definition will be essential for the alternative gene therapy approaches based on modulation of splicing to bypass DMD-causing mutations in the endogenous dystrophin gene.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-425" status="OLD">
          <idno type="ISNI">0000000098865504</idno>
          <idno type="RNSR">201722404H</idno>
          <idno type="ROR">https://ror.org/05ee10k25</idno>
          <orgName>Institut de génétique humaine</orgName>
          <orgName type="acronym">IGH</orgName>
          <date type="start">1998-01-01</date>
          <date type="end">2021-12-31</date>
          <desc>
            <address>
              <addrLine>institut de Génétique humaine 141 Rue de la Cardonille 34396 MONTPELLIER CEDEX 5</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.igh.cnrs.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-410122" type="direct"/>
            <relation name="UMR9002 / UPR1142" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="laboratory" xml:id="struct-1047" status="OLD">
          <orgName>Institut de génétique et biologie moléculaire et cellulaire</orgName>
          <orgName type="acronym">IGBMC</orgName>
          <date type="end">2008-12-31</date>
          <desc>
            <address>
              <addrLine>I.G.B.M.C, Parc D'Innovation 1 Rue Laurent Fries - BP 10142 67404 ILLKIRCH CEDEX</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www-ulp.u-strasbg.fr/unite_recherche.php?u=14</ref>
          </desc>
          <listRelation>
            <relation active="#struct-300320" type="direct"/>
            <relation name="U596" active="#struct-303623" type="direct"/>
            <relation name="UMR7104" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-410122" status="OLD">
          <idno type="ISNI">0000000120970141</idno>
          <idno type="ROR">https://ror.org/051escj72</idno>
          <orgName>Université de Montpellier</orgName>
          <orgName type="acronym">UM</orgName>
          <date type="end">2021-12-31</date>
          <desc>
            <address>
              <addrLine>163 rue Auguste Broussonnet - 34090 Montpellier</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.umontpellier.fr/</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-300320" status="OLD">
          <orgName>Université Louis Pasteur - Strasbourg I</orgName>
          <date type="start">1970-01-01</date>
          <date type="end">2009-01-01</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
          </desc>
        </org>
        <org type="institution" xml:id="struct-303623" status="VALID">
          <idno type="IdRef">026388278</idno>
          <idno type="ROR">https://ror.org/02vjkv261</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>
            <address>
              <addrLine>101, rue de Tolbiac, 75013 Paris</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>