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

International Journal of Molecular Sciences
Isabel Gómez-RedondoAlfonso Gutiérrez-Adán

Abstract

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 cel...Continue Reading

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Citations

May 1, 2021·International Journal of Molecular Sciences·Eva PericuestaAlfonso Gutiérrez-Adán
Aug 31, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Maria-Luisa Del RioJose-Ignacio Rodriguez-Barbosa

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Datasets Mentioned

BETA
E-MTAB-9102

Methods Mentioned

BETA
transgenic
RNA-seq
flow cytometry
PCR
RNA Assay

Software Mentioned

HTSeq
house Perl scripts
custom
count
STAR
ArrayExpress
in
DESeq2
Bioconductor package
RSEM

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