{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:48Z","timestamp":1786978188617,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS112687"],"award-info":[{"award-number":["NS112687"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS122756"],"award-info":[{"award-number":["NS122756"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS112796"],"award-info":[{"award-number":["NS112796"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS093287"],"award-info":[{"award-number":["NS093287"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS113820"],"award-info":[{"award-number":["NS113820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM136897"],"award-info":[{"award-number":["GM136897"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the\n                      <jats:italic>PPP2R2B<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      In this study, we tested the hypothesis that the\n                      <jats:italic>PPP2R2B antisense<\/jats:italic>\n                      (\n                      <jats:italic>PPP2R2B\u2010AS1<\/jats:italic>\n                      ) transcript containing a CUG repeat is expressed and contributes to SCA12 pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Expression of\n                      <jats:italic>PPP2R2B\u2010AS1<\/jats:italic>\n                      transcript was detected in SCA12 human induced pluripotent stem cells (iPSCs), iPSC\u2010derived NGN2 neurons, and SCA12 knock\u2010in mouse brains using strand\u2010specific reverse transcription polymerase chain reaction. The tendency of expanded\n                      <jats:italic>PPP2R2B\u2010AS1<\/jats:italic>\n                      (\n                      <jats:italic>expPPP2R2B\u2010AS1<\/jats:italic>\n                      ) RNA to form foci, a marker of toxic processes involving mutant RNAs, was examined in SCA12 cell models by fluorescence in situ hybridization. The apoptotic effect of\n                      <jats:italic>expPPP2R2B\u2010AS1<\/jats:italic>\n                      transcripts on SK\u2010N\u2010MC neuroblastoma cells was evaluated by caspase 3\/7 activity. Western blot was used to examine the expression of repeat associated non\u2010ATG\u2010initiated translation of\n                      <jats:italic>expPPP2R2B\u2010AS1<\/jats:italic>\n                      transcript in SK\u2010N\u2010MC cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The repeat region in the\n                      <jats:italic>PPP2R2B<\/jats:italic>\n                      gene locus is bidirectionally transcribed in SCA12 iPSCs, iPSC\u2010derived NGN2 neurons, and SCA12 mouse brains. Transfected\n                      <jats:italic>expPPP2R2B\u2010AS1<\/jats:italic>\n                      transcripts induce apoptosis in SK\u2010N\u2010MC cells, and the apoptotic effect may be mediated, at least in part, by the RNA secondary structure. The\n                      <jats:italic>expPPP2R2B\u2010AS1<\/jats:italic>\n                      transcripts form CUG RNA foci in SK\u2010N\u2010MC cells.\n                      <jats:italic>expPPP2R2B\u2010AS1<\/jats:italic>\n                      transcript is translated in the alanine open reading frame (ORF) via repeat\u2010associated non\u2010ATG translation, which is diminished by single\u2010nucleotide interruptions within the CUG repeat and MBNL1 overexpression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that\n                      <jats:italic>PPP2R2B\u2010AS1<\/jats:italic>\n                      contributes to SCA12 pathogenesis and may therefore provide a novel therapeutic target for the disease. \u00a9 2023 International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.29605","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T02:16:04Z","timestamp":1695348964000},"page":"2230-2240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bidirectional Transcription at the\n                    <scp>\n                      <i>PPP2R2B<\/i>\n                    <\/scp>\n                    Gene Locus in Spinocerebellar Ataxia Type 12"],"prefix":"10.1002","volume":"38","author":[{"given":"Chengqian","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans B.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Jahanbakhsh","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry Johns Hopkins University  Baltimore Maryland USA"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyao","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Hugo W. 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