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dc.contributor.author
Maslon, M.
dc.contributor.author
Braunschweig, U.
dc.contributor.author
Aitken, S.
dc.contributor.author
Mann, A.R.
dc.contributor.author
Kilanowski, F.
dc.contributor.author
Hunter, C.H.
dc.contributor.author
Blencowe, B.J.
dc.contributor.author
Kornblihtt, Alberto Rodolfo
dc.contributor.author
Adams, I.
dc.contributor.author
Cáceres, J.F.
dc.date.available
2021-01-22T14:40:52Z
dc.date.issued
2019-04
dc.identifier.citation
Maslon, M.; Braunschweig, U.; Aitken, S.; Mann, A.R.; Kilanowski, F.; et al.; A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes; Nature Publishing Group; Embo Journal; 38; 9; 4-2019; 1-18
dc.identifier.issn
0261-4189
dc.identifier.uri
http://hdl.handle.net/11336/123460
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ESCS DIFFERENTIATION
dc.subject
KINETIC COUPLING
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MOUSE MODEL
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RNA POLYMERASE II
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TRANSCRIPTION ELONGATION
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-13T20:42:52Z
dc.journal.volume
38
dc.journal.number
9
dc.journal.pagination
1-18
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Maslon, M.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Braunschweig, U.. University of Toronto; Canadá
dc.description.fil
Fil: Aitken, S.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Mann, A.R.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Kilanowski, F.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Hunter, C.H.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Blencowe, B.J.. University of Toronto; Canadá
dc.description.fil
Fil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Adams, I.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Cáceres, J.F.. University of Edinburgh; Reino Unido
dc.journal.title
Embo Journal
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.15252/embj.2018101244
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