{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T01:11:01Z","timestamp":1782090661552,"version":"3.54.5"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB958 to B.J.E. and TRR186\/A15 to F.H."],"award-info":[{"award-number":["SFB958 to B.J.E. and TRR186\/A15 to F.H."]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006188","name":"Einstein Stiftung Berlin","doi-asserted-by":"publisher","award":["EVF-2020-571 to B.J.E"],"award-info":[{"award-number":["EVF-2020-571 to B.J.E"]}],"id":[{"id":"10.13039\/501100006188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Phosphatase and tensin homologue (PTEN) is the main antagonist of the phosphatidylinositol-3-kinase (PI3K)\/AKT\/mTOR signalling pathway and mutated in 10%\u201320% of individuals with autism spectrum disorder (ASD) exhibiting macrocephaly. Hyperactive mTOR signalling is responsible for some aspects during PTEN-ASD progression, e.g. neuronal hypertrophy and -excitability, but PI3K\/mTOR-independent processes have additionally been described. There is emerging evidence that PTEN regulates gene transcription, spliceosome formation and pre-mRNA splicing independently of PI3K\/mTOR. Altered splicing is a hallmark of brains from individuals with idiopathic and PTEN-ASD, however, molecular mechanisms are yet to be identified.<\/jats:p>\n               <jats:p>We performed RNA-sequencing (RNA-Seq), followed by analysis of altered transcript splicing in Pten-deficient primary cortical mouse neurons, which we compared with published data from PTEN-deficient human neuronal stem cells. This analysis identified that transcripts were globally mis-spliced in a developmentally regulated fashion and cluster in synaptic and gene expression regulatory processes. Strikingly, splicing defects following Pten-deficiency represent a significant number of other known ASD-susceptibility genes. Furthermore, we show that exons with strong 3\u2032 splice sites are more frequently mis-spliced under Pten-deficient conditions. Our study indicates that PTEN-ASD is a multifactorial condition involving the dysregulation of other known ASD-susceptibility genes.<\/jats:p>","DOI":"10.1093\/brain\/awae306","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T07:26:59Z","timestamp":1727335619000},"page":"47-54","source":"Crossref","is-referenced-by-count":8,"title":["PTEN controls alternative splicing of autism spectrum disorder-associated transcripts in primary neurons"],"prefix":"10.1093","volume":"148","author":[{"given":"Sebastian","family":"Rademacher","sequence":"first","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Molecular Biology and Biochemistry , Berlin 10117 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-0844","authenticated-orcid":false,"given":"Marco","family":"Preu\u00dfner","sequence":"additional","affiliation":[{"name":"Freie Universit\u00e4t Berlin, Institute of Chemistry and Biochemistry , Berlin 14195 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie C","family":"Rehm","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Molecular Biology and Biochemistry , Berlin 10117 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Molecular Biology and Biochemistry , Berlin 10117 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-9882","authenticated-orcid":false,"given":"Florian","family":"Heyd","sequence":"additional","affiliation":[{"name":"Freie Universit\u00e4t Berlin, Institute of Chemistry and Biochemistry , Berlin 14195 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7873-8687","authenticated-orcid":false,"given":"Britta J","family":"Eickholt","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Molecular Biology and Biochemistry , Berlin 10117 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