دورية أكاديمية
أعرض في EDS

A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes.

التفاصيل البيبلوغرافية
العنوان: A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes.
المؤلفون: Maslon MM; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Braunschweig U; Donnelly Centre, Department of Molecular Genetics University of Toronto, Toronto, ON, Canada., Aitken S; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Mann AR; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Kilanowski F; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Hunter CJ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Blencowe BJ; Donnelly Centre, Department of Molecular Genetics University of Toronto, Toronto, ON, Canada., Kornblihtt AR; Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina., Adams IR; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK ian.adams@igmm.ed.ac.uk javier.caceres@igmm.ed.ac.uk., Cáceres JF; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK ian.adams@igmm.ed.ac.uk javier.caceres@igmm.ed.ac.uk.
المصدر: The EMBO journal [EMBO J] 2019 May 02; Vol. 38 (9). Date of Electronic Publication: 2019 Apr 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
أسماء مطبوعة: Publication: 2014- : London : Wiley Blackwell
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
مواضيع طبية MeSH: Alternative Splicing* , Gene Expression Regulation* , Transcription, Genetic*, Embryonic Stem Cells/*pathology , Neural Stem Cells/*metabolism , RNA Polymerase II/*genetics , RNA Polymerase II/*metabolism, Animals ; Cell Lineage ; Cells, Cultured ; Embryonic Stem Cells/metabolism ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Neural Stem Cells/pathology
مستخلص: The rate of RNA polymerase II (RNAPII) elongation has an important role in the control of alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked in for a slow elongating form of RNAPII We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice. Focusing on neuronal differentiation as a model, we observed that slow elongation impairs development of the neural lineage from ESCs, which is accompanied by changes in AS and in gene expression along this pathway. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is greater in ESC-differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development.
(© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
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معلومات مُعتمدة: United Kingdom Wellcome Trust; MC_UU_00007/6 United Kingdom MRC_ Medical Research Council; MC_UU_00007/7 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: ESCs differentiation; RNA polymerase II; kinetic coupling; mouse model; transcription elongation
المشرفين على المادة: EC 2.7.7.- (RNA Polymerase II)
تواريخ الأحداث: Date Created: 20190417 Date Completed: 20200106 Latest Revision: 20220129
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6484407
DOI: 10.15252/embj.2018101244
PMID: 30988016
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2075
DOI:10.15252/embj.2018101244