{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:56:30Z","timestamp":1787021790753,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010988","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000}}],"reference-count":97,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004004","name":"Universit\u00e0 degli Studi di Trento","doi-asserted-by":"publisher","award":["Institutional money"],"award-info":[{"award-number":["Institutional money"]}],"id":[{"id":"10.13039\/501100004004","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009836","name":"Huntington Society of Canada","doi-asserted-by":"publisher","award":["New Pathways award"],"award-info":[{"award-number":["New Pathways award"]}],"id":[{"id":"10.13039\/100009836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["NS049206"],"award-info":[{"award-number":["NS049206"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["706567"],"award-info":[{"award-number":["706567"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Alternative splicing (AS) appears to be altered in Huntington\u2019s disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of\n                    <jats:italic>Htt<\/jats:italic>\n                    CAG knock-in mouse\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models, we demonstrate a correlation between\n                    <jats:italic>Htt<\/jats:italic>\n                    CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and,\n                    <jats:italic>in vivo<\/jats:italic>\n                    , the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD). The expanded\n                    <jats:italic>Htt<\/jats:italic>\n                    CAG repeats further reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors. Integrative transcriptomic analyses unveil a network of transcriptionally altered micro-RNAs and RNA-binding proteins (Celf, hnRNPs, Ptbp, Srsf, Upf1, Ythd2) which might influence the AS machinery, primarily in neural cells. We suggest that this unbalanced expression of linear and circular RNAs might alter neural fitness, contributing to HD pathogenesis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010988","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T13:38:35Z","timestamp":1697204315000},"page":"e1010988","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["CAG repeat expansion in the Huntington\u2019s disease gene shapes linear and circular RNAs biogenesis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-4648","authenticated-orcid":true,"given":"Dilara","family":"Ayyildiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guendalina","family":"Bergonzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-1986","authenticated-orcid":true,"given":"Alan","family":"Monziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takshashila","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"D\u00f6ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2243-629X","authenticated-orcid":true,"given":"Emanuela","family":"Kerschbamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Di Leva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5319-2697","authenticated-orcid":true,"given":"Elia","family":"Pennati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0667-2396","authenticated-orcid":true,"given":"Luisa","family":"Donini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kovalenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3151-6443","authenticated-orcid":true,"given":"Jacopo","family":"Zasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-9846","authenticated-orcid":true,"given":"Luciano","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa C.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-6311","authenticated-orcid":true,"given":"Christoph","family":"Dieterich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Piazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4487-0449","authenticated-orcid":true,"given":"Erik","family":"Dassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8295-8025","authenticated-orcid":true,"given":"Marta","family":"Biagioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"pgen.1010988.ref001","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes. 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