| Title: |
New insights into minor splicing-a transcriptomic analysis of cells derived from TALS patients |
| Authors: |
Cologne, Audric; Benoit-Pilven, Clara; Besson, Alicia; Putoux, Audrey; Campan-Fournier, Amandine; Bober, Michael, B; de Die-Smulders, Christine, E.; Paulussen, Aimee; Pinson, Lucile; Toutain, Annick; Roifman, Chaim, M; Leutenegger, Anne-Louise; Mazoyer, Sylvie; Edery, Patrick; Lacroix, Vincent |
| Contributors: |
Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE); Centre Inria de l'Université Grenoble Alpes; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria); Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Genetics of Neurodevelopment (CRNL-GENDEV); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL); Hospices Civils de Lyon (HCL); Nemours/Alfred I. du Pont Hospital for Children; Maastricht University Medical Centre (MUMC); Maastricht University Maastricht; Service de génétique médicale Montpellier; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Hôpital Arnaud de Villeneuve CHU Montpellier; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Centre d’Investigation Clinique CHRU Tours (CIC 1415); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM); Imaging, Brain & Neuropsychiatry (iBraiN); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Department of Immunology; University of Toronto; Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM); Baobab LBBE; Département PEGASE LBBE (PEGASE); Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE); Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE); Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS); ANR-16-CE23-0001,ASTER,Algorithmes et outils logiciels pour le séquençage d'ARN de troisième génération(2016); ANR-18-CE12-0007,U4ATAC-BRAIN,Rôle de l'épissage mineur dans le développement cérébral(2018) |
| Source: |
ISSN: 1355-8382. |
| Publisher Information: |
CCSD; Cold Spring Harbor Laboratory Press |
| Publication Year: |
2019 |
| Collection: |
Université François-Rabelais de Tours: HAL |
| Subject Terms: |
MOPD1; U12-type introns; intron retention; RNA sequencing; minor splicing; RNU4ATAC; [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Description: |
International audience ; Minor intron splicing plays a central role in human embryonic development and survival. Indeed, biallelic mutations in RNU4ATAC, transcribed into the minor spliceosomal U4atac snRNA, are responsible for three rare autosomal recessive multimalformation disorders named Taybi-Linder (TALS/MOPD1), Roifman (RFMN), and Lowry-Wood (LWS) syndromes, which associate numerous overlapping signs of varying severity. Although RNA-seq experiments have been conducted on a few RFMN patient cells, none have been performed in TALS, and more generally no in-depth transcriptomic analysis of the ∼700 human genes containing a minor (U12-type) intron had been published as yet. We thus sequenced RNA from cells derived from five skin, three amniotic fluid, and one blood biosamples obtained from seven unrelated TALS cases and from age-and sex-matched controls. This allowed us to describe for the first time the mRNA expression and splicing profile of genes containing U12-type introns, in the context of a functional minor spliceosome. Concerning RNU4ATAC-mutated patients, we show that as expected, they display distinct U12-type intron splicing profiles compared to controls, but that rather unexpectedly mRNA expression levels are mostly unchanged. Furthermore, although U12-type intron missplicing concerns most of the expressed U12 genes, the level of U12-type intron retention is surprisingly low in fibroblasts and amniocytes, and much more pronounced in blood cells. Interestingly, we found several occurrences of introns that can be spliced using either U2, U12, or a combination of both types of splice site consensus sequences, with a shift towards splicing using preferentially U2 sites in TALS patients' cells compared to controls. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/31175170; PUBMED: 31175170 |
| DOI: |
10.1261/rna.071423.119 |
| Availability: |
https://inria.hal.science/hal-02305628; https://inria.hal.science/hal-02305628v1/document; https://inria.hal.science/hal-02305628v1/file/RNA-2019-Cologne-1130-49.pdf; https://doi.org/10.1261/rna.071423.119 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.5BF7A8AD |
| Database: |
BASE |