{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:39:30Z","timestamp":1791207570400,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,9,22]],"date-time":"2013-09-22T00:00:00Z","timestamp":1379808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>To explore the molecular pathogenesis of amyotrophic lateral sclerosis (<jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>), the nuclear function of <jats:styled-content style=\"fixed-case\">TAR\u2010DNA<\/jats:styled-content> binding protein 43\u2009kDa (<jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content>\u201043) must be elucidated. <jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content>\u201043 is a nuclear protein that colocalizes with <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ajal body or <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>em in cultured cells. Several recent studies have reported that the decreasing number of <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ems accompanied the depletion of the causative genes for <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>, <jats:italic><jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content>\u201043<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">FUS<\/jats:styled-content><\/jats:italic>. Gems play an important role in the pathogenesis of spinal muscular atrophy. Gems are the sites of the maturation of spliceosomes, which are composed of uridylate\u2010rich (<jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">snRNAs<\/jats:styled-content> (small nuclear <jats:styled-content style=\"fixed-case\">RNAs<\/jats:styled-content>) and protein complex, small nuclear ribonuclearprotein (<jats:styled-content style=\"fixed-case\">snRNP<\/jats:styled-content>). Spliceosomes regulate the splicing of pre\u2010<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and are classified into the major or minor classes, according to the consensus sequence of acceptor and donor sites of pre\u2010<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> splicing. Although the major class of spliceosomes regulates most pre\u2010<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> splicing, minor spliceosomes also play an important role in regulating the splicing or global speed of pre\u2010<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> processing. A mouse model of spinal muscular atrophy, in which the number of Gems is decreased, shows fewer subsets <jats:styled-content style=\"fixed-case\">U snRNAs<\/jats:styled-content>. Interestingly, in the central nervous system, <jats:styled-content style=\"fixed-case\">U snRNAs<\/jats:styled-content> belonging to the minor spliceosomes are markedly reduced. In <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>, the <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>12 <jats:styled-content style=\"fixed-case\">snRNA<\/jats:styled-content> is decreased only in the tissue affected by <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> and not in other tissues. Although the molecular mechanisms underlying the decreased <jats:styled-content style=\"fixed-case\">U12 snRNA<\/jats:styled-content> resulting in cell dysfunction and cell death in motor neuron diseases remain unclear, these findings suggest that the disturbance of nuclear bodies and minor splicing may underlie the common molecular pathogenesis of motor neuron diseases.<\/jats:p>","DOI":"10.1111\/neup.12070","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T22:08:01Z","timestamp":1381529281000},"page":"99-107","source":"Crossref","is-referenced-by-count":9,"title":["Minor splicing pathway is not minor any more: Implications for the pathogenesis of motor neuron diseases"],"prefix":"10.1111","volume":"34","author":[{"given":"Osamu","family":"Onodera","sequence":"first","affiliation":[{"name":"Department of Molecular Neuroscience Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Shiga","sequence":"additional","affiliation":[{"name":"Department of Pathology Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ariizumi","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Yokoseki","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoyo","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135722"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.043"},{"key":"e_1_2_11_4_1","first-page":"437","article-title":"Cajal's contribution to the knowledge of the neuronal cell nucleus. 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