Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion

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Main Authors: Gómez-Redondo, Isabel, Ramos Ibeas, Priscila, Pericuesta Camacho, Eva, Fernández González, Raúl, Laguna-Barraza, Ricardo, Gutiérrez-Adán, Alfonso
Other Authors: Ministerio de Economía y Competitividad (España)
Format: artículo biblioteca
Language:English
Published: Multidisciplinary Digital Publishing Institute 2020-06-09
Subjects:2C-like cells, U12 introns, Zrsr1, Zrsr2, Zygotic gene activation,
Online Access:http://hdl.handle.net/10261/340397
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/501100011033
https://api.elsevier.com/content/abstract/scopus_id/85086221685
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spelling dig-inia-es-10261-3403972024-05-17T20:41:07Z Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion Gómez-Redondo, Isabel Ramos Ibeas, Priscila Pericuesta Camacho, Eva Fernández González, Raúl Laguna-Barraza, Ricardo Gutiérrez-Adán, Alfonso Ministerio de Economía y Competitividad (España) Agencia Estatal de Investigación (España) Comunidad de Madrid Ministerio de Ciencia, Innovación y Universidades (España) Gómez-Redondo, Isabel [0000-0002-9319-7580] Ramos Ibeas, Priscila [0000-0003-4578-0189] Pericuesta Camacho, Eva [0000-0001-9387-3270] Fernández González, Raúl [0000-0003-1989-2945] Gutiérrez-Adán, Alfonso [0000-0001-9893-9179] 2C-like cells U12 introns Zrsr1 Zrsr2 Zygotic gene activation 15 Pág. Minor splicing plays an important role in vertebrate development. Zrsr1 and Zrsr2 paralog genes have essential roles in alternative splicing, mainly participating in the recognition of minor (U12) introns. To further explore their roles during early embryo development, we produced Zrsr1mu and Zrsr2mu mutant mice, containing truncating mutations within the second zinc finger domain. Both homozygous mutant mice were viable with a normal lifespan. When we crossed a homozygous Zrsr2mu/mu female with Zrsr1mu/mu male, the double heterozygotes were non-viable, giving rise to embryos that stopped developing mainly between the 2- and 4-cell stages, just after zygotic gene activation. RNA-seq analysis of Zrsr1/2mu 2-cell embryos showed altered gene and isoform expression of thousands of genes enriched in gene ontology terms and biological pathways related to ribosome, RNA transport, spliceosome, and essential zygotic gene activation steps. Alternative splicing was analyzed, showing a significant increase in intron retention in both U2 and U12 intron-containing genes related to cell cycle and mitotic nuclear division. Remarkably, both Zrsr1 and Zrsr2 were required for the conversion of mouse-induced pluripotent stem cells into 2C-like cells. According to our results, Zrsr1 or Zrsr2 are necessary for ZGA and both are indispensable for the conversion of induced pluripotent stem cells into 2C-like cells. This work was funded by grants AGL2015-66145-R and RTI2018-093548-B-I00 from the Spanish Ministry of Science and Innovation. I.G.-R. was supported by a predoctoral fellowship from the same ministry (BES-2016- 077794). P.R.-I. was supported by a Talent Attraction Postdoctoral Fellowship from the Madrid Community (2017-T2/BIO-5182) and by a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation (RYC2018-025666-I). Peer reviewed 2023-12-11T10:24:40Z 2023-12-11T10:24:40Z 2020-06-09 artículo http://purl.org/coar/resource_type/c_6501 International Journal of Molecular Sciences 21(11): 1-15 (2020) 1661-6596 http://hdl.handle.net/10261/340397 10.3390/ijms21114115 1422-0067 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100011033 32527007 2-s2.0-85086221685 https://api.elsevier.com/content/abstract/scopus_id/85086221685 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/MINECO//AGL2015-66145-R/ES/FUNCION DEL PROCESAMIENTO ALTERNATIVO DEL PRE-ARNM EN LA REGULACION DEL DESARROLLO EMBRIONARIO, DETERMINACION DEL SEXO, FERTILIDAD Y ADAPTACION/ info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-093548-B-I00/ES/ANALISIS FUNCIONAL DE ISOFORMAS DE ARNM RELACIONADAS CON DESARROLLO EMBRIONARIO Y FERTILIDAD/ info:eu-repo/grantAgreement/MINECO//BES-2016-077794 S2017-T2/BIO-5182 info:eu-repo/grantAgreement/MICIU//RYC2018-025666-I Departamento de Reproducción Animal​  Publisher's version https://doi.org/10.3390/ijms21114115 Sí open application/pdf Multidisciplinary Digital Publishing Institute
institution INIA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-inia-es
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region Europa del Sur
libraryname Biblioteca del INIA España
language English
topic 2C-like cells
U12 introns
Zrsr1
Zrsr2
Zygotic gene activation
2C-like cells
U12 introns
Zrsr1
Zrsr2
Zygotic gene activation
spellingShingle 2C-like cells
U12 introns
Zrsr1
Zrsr2
Zygotic gene activation
2C-like cells
U12 introns
Zrsr1
Zrsr2
Zygotic gene activation
Gómez-Redondo, Isabel
Ramos Ibeas, Priscila
Pericuesta Camacho, Eva
Fernández González, Raúl
Laguna-Barraza, Ricardo
Gutiérrez-Adán, Alfonso
Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
description 15 Pág.
author2 Ministerio de Economía y Competitividad (España)
author_facet Ministerio de Economía y Competitividad (España)
Gómez-Redondo, Isabel
Ramos Ibeas, Priscila
Pericuesta Camacho, Eva
Fernández González, Raúl
Laguna-Barraza, Ricardo
Gutiérrez-Adán, Alfonso
format artículo
topic_facet 2C-like cells
U12 introns
Zrsr1
Zrsr2
Zygotic gene activation
author Gómez-Redondo, Isabel
Ramos Ibeas, Priscila
Pericuesta Camacho, Eva
Fernández González, Raúl
Laguna-Barraza, Ricardo
Gutiérrez-Adán, Alfonso
author_sort Gómez-Redondo, Isabel
title Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
title_short Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
title_full Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
title_fullStr Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
title_full_unstemmed Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion
title_sort minor splicing factors zrsr1 and zrsr2 are essential for early embryo development and 2-cell-like conversion
publisher Multidisciplinary Digital Publishing Institute
publishDate 2020-06-09
url http://hdl.handle.net/10261/340397
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/501100011033
https://api.elsevier.com/content/abstract/scopus_id/85086221685
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