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Minor Splicing Factors Zrsr1 and Zrsr2 Essential for Gametogenesis, Early Embryo Development and Conversion of Stem Cells into 2C-Like

46 Pages Posted: 8 Apr 2019 Sneak Peek Status: Under Review

See all articles by Isabel Gómez-Redondo

Isabel Gómez-Redondo

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Priscila Ramos-Ibeas

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Eva Pericuesta

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Benjamín Planells

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Raul Fernández-González

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Ricardo Laguna-Barraza

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Serafín Perez-Cerezales

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

Keiko Horiuchi

Nippon Medical School - Department of Protein-Protein Interaction Research

Alfonso Gutierrez-Adan

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

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Abstract

Zrsr2 has been attributed a role in splice site recognition of U12 and U2 introns. To better understand the part played by minor splicing during oogenesis and early embryo development, we produced Zrsr2 mutant mice (Zrsr2mu). In Zrsr2mu female oogenesis was blocked at the secondary follicle stage, in a similar way as Zrsr1mu affects spermatogenesis. Zrsr2mu follicles showed altered expression of genes related to gonad development, DNA replication and cell cycle regulation, and altered splicing events involving enrichment of U12-type intron retention (IR). Embryo development was impaired during zygotic gene activation (ZGA) at the 2-cell stage when female Zrsr2mu were crossed with male Zrsr1mu. These embryos showed increased IR in U12-containing genes related to the cell cycle and mitotic nuclear division. Remarkably, both mouse Zrsr1 and Zrsr2 were required for conversion of mouse induced pluripotent stem cells (iPSC) into 2C-like cells. According to our results, Zrsr1 and Zrsr2 are essential during overall chromatin reorganization in the meiotic prophase of meiosis, ZGA and conversion of pluripotent into 2C-like cells.

Keywords: Zrsr1, Zrsr2, U12 introns, gametogenesis, zygotic gene activation, 2C-like cells 20 2

Suggested Citation

Gómez-Redondo, Isabel and Ramos-Ibeas, Priscila and Pericuesta, Eva and Planells, Benjamín and Fernández-González, Raul and Laguna-Barraza, Ricardo and Perez-Cerezales, Serafín and Horiuchi, Keiko and Gutierrez-Adan, Alfonso, Minor Splicing Factors Zrsr1 and Zrsr2 Essential for Gametogenesis, Early Embryo Development and Conversion of Stem Cells into 2C-Like (April 6, 2019). Available at SSRN: https://ssrn.com/abstract=3367197 or http://dx.doi.org/10.2139/ssrn.3367197
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Isabel Gómez-Redondo

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Priscila Ramos-Ibeas

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Eva Pericuesta

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Benjamín Planells

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Raul Fernández-González

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Ricardo Laguna-Barraza

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Serafín Perez-Cerezales

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal

28040 Madrid
Spain

Keiko Horiuchi

Nippon Medical School - Department of Protein-Protein Interaction Research

Japan

Alfonso Gutierrez-Adan (Contact Author)

Instituto Nacional de Investigación y Tecnologia Agraria - Departamento de Reproducción Animal ( email )

28040 Madrid
Spain

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