Natural SINEUP RNAs in Autism Spectrum Disorders
| العنوان: | Natural SINEUP RNAs in Autism Spectrum Disorders |
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| المؤلفون: | Giulia Zarantonello, Michele Arnoldi, Michele Filosi, Toma Tebaldi, Giovanni Spirito, Anna Barbieri, Stefano Gustincich, Remo Sanges, Enrico Domenici, Francesca Di Leva, Marta Biagioli |
| المصدر: | Frontiers in Genetics Frontiers in Genetics, Vol 12 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Microcephaly, neurodeveloment, QH426-470, Biology, lncRNA, CHD8, SINEUP, Settore BIO/13 - Biologia Applicata, medicine, Genetics, Post-transcriptional regulation, Gene, Genetics (clinical), autism spectrum disorders (ASD), RAB11 GTPase, RNA, Translation (biology), Brief Research Report, natural antisense transcript (NAT), post-transcriptional regulation, medicine.disease, Phenotype, Autism, Molecular Medicine, Haploinsufficiency |
| الوصف: | CHD8 represents one of the highest confidence genetic risk factors implied in Autism Spectrum Disorders, with most mutations leading to CHD8 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 CHD8 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 CHD8 knock down (KD), we first identified RAB11B-AS1 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 CHD8 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. |
| تدمد: | 1664-8021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2726c354a2d34f18587bee981a100096Test https://pubmed.ncbi.nlm.nih.gov/34880900Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2726c354a2d34f18587bee981a100096 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16648021 |
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