Antisense Transcription in Loci Associated to Hereditary Neurodegenerative Diseases
| العنوان: | Antisense Transcription in Loci Associated to Hereditary Neurodegenerative Diseases |
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| المؤلفون: | Stefania Fedele, Francesca Persichetti, Raffaella Calligaris, Claudio Santoro, Piero Carninci, Yoshihide Hayashizaki, Silvia Zucchelli, Peter Heutink, Stefano Gustincich, Hideya Kawaji, Alistair R. R. Forrest, Timo Lassmann, Masayoshi Itoh, Patrizia Rizzu, Paolo Vatta |
| المساهمون: | Human genetics |
| المصدر: | Molecular Neurobiology Molecular neurobiology 56(8), 5392-5415 (2019). doi:10.1007/s12035-018-1465-2 Molecular Neurobiology, 56(8), 5392-5415. Humana Press Zucchelli, S, Fedele, S, Vatta, P, Calligaris, R, Heutink, P, Rizzu, P, Itoh, M, Persichetti, F, Santoro, C, Kawaji, H, Lassmann, T, Hayashizaki, Y, Carninci, P, Forrest, A R R, Gustincich, S & FANTOM Consortium 2019, ' Antisense Transcription in Loci Associated to Hereditary Neurodegenerative Diseases ', Molecular Neurobiology, vol. 56, no. 8, pp. 5392-5415 . https://doi.org/10.1007/s12035-018-1465-2 |
| بيانات النشر: | Springer US, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, Neuroscience (miscellaneous), genetics [RNA, Long Noncoding], Computational biology, Biology, metabolism [RNA, Messenger], Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, genetics [RNA, Messenger], 0302 clinical medicine, ddc:570, Antisense transcription, Cell Line, Tumor, Gene expression, medicine, Humans, Genetic Predisposition to Disease, RNA, Antisense, RNA, Messenger, Gene, Regulation of gene expression, Neurodegeneration, Neurodegenerative diseases, Promoter, Genetic Pleiotropy, Molecular Sequence Annotation, medicine.disease, Cap analysis gene expression, Long non-coding RNA, Antisense Orientation, 030104 developmental biology, Neurology, Gene Expression Regulation, Genetic Loci, genetics [Neurodegenerative Diseases], metabolism [RNA, Long Noncoding], RNA, Long Noncoding, genetics [RNA, Antisense], 030217 neurology & neurosurgery, Long noncoding RNA |
| الوصف: | Natural antisense transcripts are common features of mammalian genes providing additional regulatory layers of gene expression. A comprehensive description of antisense transcription in loci associated to familial neurodegenerative diseases may identify key players in gene regulation and provide tools for manipulating gene expression. We take advantage of the FANTOM5 sequencing datasets that represent the largest collection to date of genome-wide promoter usage in almost 2000 human samples. Transcription start sites (TSSs) are mapped at high resolution by the use of a modified protocol of cap analysis of gene expression (CAGE) for high-throughput single molecule next-generation sequencing with Helicos (hCAGE). Here we present the analysis of antisense transcription at 17 loci associated to hereditary Alzheimer’s disease, Frontotemporal Dementia, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Huntington’s disease. We focused our analysis on libraries derived from brain tissues and primary cells. We also screened libraries from total blood and blood cell populations in the quest for peripheral biomarkers of neurodegenerative diseases. We identified 63 robust promoters in antisense orientation to genes associated to familial neurodegeneration. When applying a less stringent cutoff, this number increases to over 400. A subset of these promoters represents alternative TSSs for 24 FANTOM5 annotated long noncoding RNA (lncRNA) genes, in antisense orientation to 13 of the loci analyzed here, while the remaining contribute to the expression of additional transcript variants. Intersection with GWAS studies, sample ontology, and dynamic expression reveals association to specific genetic traits as well as cell and tissue types, not limited to neurodegenerative diseases. Antisense transcription was validated for a subset of genes, including those encoding for Microtubule-Associated Protein Tau, α-synuclein, Parkinsonism-associated deglycase DJ-1, and Leucin-Rich Repeat Kinase 2. This work provides evidence for the existence of additional regulatory mechanisms of the expression of neurodegenerative disease-causing genes by previously not-annotated and/or not-validated antisense long noncoding RNAs. Electronic supplementary material The online version of this article (10.1007/s12035-018-1465-2) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1559-1182 0893-7648 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::120ea6efe086086ac3137d6fc47f8071 http://europepmc.org/articles/PMC6614138 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....120ea6efe086086ac3137d6fc47f8071 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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