{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:08:37Z","timestamp":1780762117657,"version":"3.54.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:italic>CHD8<\/jats:italic> represents one of the highest confidence genetic risk factors implied in Autism Spectrum Disorders, with most mutations leading to <jats:italic>CHD8<\/jats:italic> haploinsufficiency and the insurgence of specific phenotypes, such as macrocephaly, facial dysmorphisms, intellectual disability, and gastrointestinal complaints. While extensive studies have been conducted on the possible consequences of <jats:italic>CHD8<\/jats:italic> suppression and protein coding RNAs dysregulation during neuronal development, the effects of transcriptional changes of long non-coding RNAs (lncRNAs) remain unclear. In this study, we focused on a peculiar class of natural antisense lncRNAs, SINEUPs, that enhance translation of a target mRNA through the activity of two RNA domains, an embedded transposable element sequence and an antisense region. By looking at dysregulated transcripts following <jats:italic>CHD8<\/jats:italic> knock down (KD), we first identified <jats:italic>RAB11B-AS1<\/jats:italic> as a potential SINEUP RNA for its domain configuration. Then we demonstrated that such lncRNA is able to increase endogenous RAB11B protein amounts without affecting its transcriptional levels. RAB11B has a pivotal role in vesicular trafficking, and mutations on this gene correlate with intellectual disability and microcephaly. Thus, our study discloses an additional layer of molecular regulation which is altered by <jats:italic>CHD8<\/jats:italic> suppression. This represents the first experimental confirmation that naturally occurring SINEUP could be involved in ASD pathogenesis and underscores the importance of dysregulation of functional lncRNAs in neurodevelopment.<\/jats:p>","DOI":"10.3389\/fgene.2021.745229","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T10:05:20Z","timestamp":1638266720000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Natural SINEUP RNAs in Autism Spectrum Disorders: RAB11B-AS1 Dysregulation in a Neuronal CHD8 Suppression Model Leads to RAB11B Protein Increase"],"prefix":"10.3389","volume":"12","author":[{"given":"Giulia","family":"Zarantonello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Arnoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Filosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toma","family":"Tebaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Spirito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gustincich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo","family":"Sanges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Domenici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Di Leva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Biagioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/2040-2392-4-36","article-title":"SFARI Gene 2.0: a Community-Driven Knowledgebase for the Autism Spectrum Disorders (ASDs)","volume":"4","author":"Abrahams","year":"2013","journal-title":"Mol. 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