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Article

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

Departamento de Reproducción Animal, INIA, Avda. Puerta de Hierro n° 12. Local 10, 28040 Madrid, Spain
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Int. J. Mol. Sci. 2020, 21(11), 4115; https://doi.org/10.3390/ijms21114115
Received: 19 May 2020 / Revised: 4 June 2020 / Accepted: 4 June 2020 / Published: 9 June 2020
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. View Full-Text
Keywords: Zrsr1; Zrsr2; U12 introns; zygotic gene activation; 2C-like cells Zrsr1; Zrsr2; U12 introns; zygotic gene activation; 2C-like cells
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MDPI and ACS Style

Gómez-Redondo, I.; Ramos-Ibeas, P.; Pericuesta, E.; Fernández-González, R.; Laguna-Barraza, R.; Gutiérrez-Adán, A. Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion. Int. J. Mol. Sci. 2020, 21, 4115. https://doi.org/10.3390/ijms21114115

AMA Style

Gómez-Redondo I, Ramos-Ibeas P, Pericuesta E, Fernández-González R, Laguna-Barraza R, Gutiérrez-Adán A. Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion. International Journal of Molecular Sciences. 2020; 21(11):4115. https://doi.org/10.3390/ijms21114115

Chicago/Turabian Style

Gómez-Redondo, Isabel, Priscila Ramos-Ibeas, Eva Pericuesta, Raúl Fernández-González, Ricardo Laguna-Barraza, and Alfonso Gutiérrez-Adán. 2020. "Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion" International Journal of Molecular Sciences 21, no. 11: 4115. https://doi.org/10.3390/ijms21114115

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