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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,7,30]]},"abstract":"<jats:p>\n                    Expansion of intronic GGGGCC repeats in the\n                    <jats:italic>C9orf72<\/jats:italic>\n                    gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Transcription of the expanded repeats results in the formation of RNA-containing nuclear foci and altered RNA metabolism. In addition, repeat-associated non-AUG (RAN) translation of the expanded GGGGCC-repeat sequence results in the production of highly toxic dipeptide-repeat (DPR) proteins. GGGGCC repeat\u2013containing transcripts form G-quadruplexes, which are associated with formation of RNA foci and RAN translation. Zfp106, an RNA-binding protein essential for motor neuron survival in mice, suppresses neurotoxicity in a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model of\n                    <jats:italic>C9orf72<\/jats:italic>\n                    ALS. Here, we show that Zfp106 inhibits formation of RNA foci and significantly reduces RAN translation caused by GGGGCC repeats in cultured mammalian cells, and we demonstrate that Zfp106 coexpression reduces the levels of DPRs in\n                    <jats:italic>C9orf72<\/jats:italic>\n                    patient-derived cells. Further, we show that Zfp106 binds to RNA G-quadruplexes and causes a conformational change in the G-quadruplex structure formed by GGGGCC repeats. Together, these data demonstrate that Zfp106 suppresses the formation of RNA foci and DPRs caused by GGGGCC repeats and suggest that the G-quadruplex RNA-binding function of Zfp106 contributes to its suppression of GGGGCC repeat-mediated cytotoxicity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2220020121","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T13:48:47Z","timestamp":1721742527000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Zfp106 binds to G-quadruplex RNAs and inhibits RAN translation and formation of RNA foci caused by G4C2 repeats"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-8155","authenticated-orcid":false,"given":"Barbara","family":"Celona","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally E.","family":"Salomonsson","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, University of California, San Francisco, CA 94143"},{"name":"Memory &amp; Aging Center, Department of Neurology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifan","family":"Wu","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California, San Francisco, CA 94143"},{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1962-8677","authenticated-orcid":false,"given":"Bobo","family":"Dang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California, San Francisco, CA 94143"},{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huong T.","family":"Kratochvil","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California, San Francisco, CA 94143"},{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-2278","authenticated-orcid":false,"given":"Claire D.","family":"Clelland","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, University of California, San Francisco, CA 94143"},{"name":"Memory &amp; Aging Center, Department of Neurology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4745-263X","authenticated-orcid":false,"given":"William 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