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The mutant ATXN2 protein with a polyglutamine tract is known to be toxic and contributes to the SCA2 pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Here, we tested the hypothesis that the mutant\n                      <jats:italic>ATXN2<\/jats:italic>\n                      transcript with an expanded CAG repeat (\n                      <jats:italic>expATXN2<\/jats:italic>\n                      ) is also toxic and contributes to SCA2 pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The toxic effect of\n                      <jats:italic>expATXN2<\/jats:italic>\n                      transcripts on SK\u2010N\u2010MC neuroblastoma cells and primary mouse cortical neurons was evaluated by caspase 3\/7 activity and nuclear condensation assay, respectively. RNA immunoprecipitation assay was performed to identify RNA binding proteins (RBPs) that bind to\n                      <jats:italic>expATXN2<\/jats:italic>\n                      RNA. Quantitative PCR was used to examine if ribosomal RNA (rRNA) processing is disrupted in SCA2 and Huntington's disease (HD) human brain tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>expATXN2<\/jats:italic>\n                      RNA induces neuronal cell death, and aberrantly interacts with RBPs involved in RNA metabolism. One of the RBPs, transducin \u03b2\u2010like protein 3 (TBL3), involved in rRNA processing, binds to both\n                      <jats:italic>expATXN2<\/jats:italic>\n                      and expanded\n                      <jats:italic>huntingtin<\/jats:italic>\n                      (\n                      <jats:italic>expHTT<\/jats:italic>\n                      ) RNA\n                      <jats:italic>in vitro<\/jats:italic>\n                      . rRNA processing is disrupted in both SCA2 and HD human brain tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings provide the first evidence of a contributory role of\n                      <jats:italic>expATXN2<\/jats:italic>\n                      transcripts in SCA2 pathogenesis, and further support the role of\n                      <jats:italic>expHTT<\/jats:italic>\n                      transcripts in HD pathogenesis. The disruption of rRNA processing, mediated by aberrant interaction of RBPs with\n                      <jats:italic>expATXN2<\/jats:italic>\n                      and\n                      <jats:italic>expHTT<\/jats:italic>\n                      transcripts, suggest a point of convergence in the pathogeneses of repeat expansion diseases with potential therapeutic implications. \u00a9 2021 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.28729","type":"journal-article","created":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T05:37:49Z","timestamp":1628919469000},"page":"2519-2529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<scp>RNA<\/scp>\n                    Toxicity and Perturbation of\n                    <scp>rRNA<\/scp>\n                    Processing in Spinocerebellar Ataxia Type\n                    <scp>2<\/scp>"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-6348","authenticated-orcid":false,"given":"Pan P.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roumita","family":"Moulick","sequence":"additional","affiliation":[{"name":"T.C. Jenkins Department of Biophysics Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Arbez","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard O.","family":"Marque","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Hedglen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-474X","authenticated-orcid":false,"given":"H.Y. Edwin","family":"Chan","sequence":"additional","affiliation":[{"name":"Biochemistry Program, School of Life Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan M.","family":"Pulst","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell L.","family":"Margolis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Division of Neurobiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Woodson","sequence":"additional","affiliation":[{"name":"T.C. 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