{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:34:46Z","timestamp":1791268486358,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T00:00:00Z","timestamp":1366588800000},"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":[[2013,12]]},"abstract":"<jats:p>Spinocerebellar ataxia type 31 (<jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content>) is an autosomal\u2010dominant cerebellar ataxia showing a Purkinje cell (<jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>)\u2010predominant neurodegeneration in humans. The mutation is a complex penta\u2010nucleotide repeat containing (<jats:styled-content style=\"fixed-case\">TGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub>, (<jats:styled-content style=\"fixed-case\">TAGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub>, (<jats:styled-content style=\"fixed-case\">TAAAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> and (<jats:styled-content style=\"fixed-case\">TAGAATAAAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> inserted in an intron shared by two different genes <jats:italic><jats:styled-content style=\"fixed-case\">BEAN1<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TK2<\/jats:styled-content><\/jats:italic> located in the long arm of the human chromosome 16. Previous studies have shown that (<jats:styled-content style=\"fixed-case\">TGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> is the critical component of <jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content> pathogenesis while the three other repeats, also present in normal Japanese, are not essential. Importantly, it has been shown that <jats:italic><jats:styled-content style=\"fixed-case\">BEAN1<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TK2<\/jats:styled-content><\/jats:italic> are transcribed in mutually opposite directions in the human brain. Furthermore, abnormal <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> structures called \u201c<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> foci\u201d are observed by a probe against (<jats:styled-content style=\"fixed-case\">UAGAAUAAAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> in <jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content> patients' <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content> nuclei, indicating that the <jats:italic><jats:styled-content style=\"fixed-case\">BEAN1<\/jats:styled-content><\/jats:italic>\u2010direction mutant transcript appears instrumental for the pathogenesis. However, it is not known whether the critical repeat (<jats:styled-content style=\"fixed-case\">TGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> contributes to the formation of <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> foci, neither do we understand how the <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> foci formation is relevant to the pathogenesis. To address these issues, we investigated two <jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content> cerebella by fluorescence <jats:italic>in situ<\/jats:italic> hybridization using a probe against (<jats:styled-content style=\"fixed-case\">UGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub>. We also asked whether the mutant <jats:italic><jats:styled-content style=\"fixed-case\">BEAN1<\/jats:styled-content><\/jats:italic>\u2010transcript containing (<jats:styled-content style=\"fixed-case\">UGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> exerts toxicity compared to the other three repeats in cultured cells. Histopathologically, we confirm that the <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content> is the main target of <jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content> pathogenesis. We find that the <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> foci containing (<jats:styled-content style=\"fixed-case\">UGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> are indeed observed in <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content> nuclei of both <jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content> patients, whereas similar foci were not observed in control individuals. In both transiently and stably expressed cultured cell models, we also find that the mutation transcribed in the <jats:italic><jats:styled-content style=\"fixed-case\">BEAN1<\/jats:styled-content><\/jats:italic>\u2010direction yields more toxicity than control transcripts and forms <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> foci detected with probes against (<jats:styled-content style=\"fixed-case\">UGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> and (<jats:styled-content style=\"fixed-case\">UAGAAUAAAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub>. Taking these findings together, we conclude that the <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> foci containing <jats:italic><jats:styled-content style=\"fixed-case\">BEAN1<\/jats:styled-content><\/jats:italic>\u2010direction transcript (<jats:styled-content style=\"fixed-case\">UGGAA<\/jats:styled-content>)<jats:sub>n<\/jats:sub> are associated with <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content> degeneration in <jats:styled-content style=\"fixed-case\">SCA31<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/neup.12032","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T07:47:04Z","timestamp":1366703224000},"page":"600-611","source":"Crossref","is-referenced-by-count":59,"title":["Abnormal <scp>RNA<\/scp> structures (<scp>RNA<\/scp> foci) containing a penta\u2010nucleotide repeat (<scp>UGGAA<\/scp>)<sub>n<\/sub> in the <scp>P<\/scp>urkinje cell nucleus is associated with spinocerebellar ataxia type 31 pathogenesis"],"prefix":"10.1111","volume":"33","author":[{"given":"Yusuke","family":"Niimi","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Department of Pathology Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Umeda","sequence":"additional","affiliation":[{"name":"Department of Pathology Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Obayashi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomu","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwa","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Eishi","sequence":"additional","affiliation":[{"name":"Department of Pathology Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehiro","family":"Mizusawa","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinya","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science Graduate School Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,4,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70183-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.019"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000173065.75680.e2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/432518"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-008-0062-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2009.44"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2010.01142.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113014"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2011.06.028"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.015"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.010"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013343108"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4072-08.2009"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0630-0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.128.6.995"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00267823"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2007.06.001"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2008.00947.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh683"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000600"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr299"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21081"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182377e3a"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fneup.12032","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T21:45:40Z","timestamp":1696283140000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,22]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["10.1111\/neup.12032"],"URL":"https:\/\/doi.org\/10.1111\/neup.12032","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,22]]}}}