ZNHIT3 regulates translation to ensure mouse preimplantation development [seRNA-Seq]

Upon fertilization, the mouse zygotic genome is activated, accompanied by degradation of maternal proteins and RNAs. The development programs are built by accumulation of proteins from zygotic genes to guide the early cell fate commitments. Box C/D snoRNA ribonucleoprotein (snoRNP) complex is required for rRNA biogenesis, ribosome assembly and pre-mRNA splicing necessary for protein translation. Zinc finger, HIT type 3 (encoded by Znhit3) was previously identified to be one component in the assembly of the box C/D snoRNP complex. Using gene-edited mice, we identify Znhit3 as a pioneer embryonic gene whose ablation prevents mouse embryos development beyond the morula stage due to reduced protein translation. Znhit3 ablation impairs snoRNA and rRNA levels which leads to defects of ribosomes and failure of mRNA splicing. Our results provide clear evidence that ZNHIT3 is required for mouse preimplantation development by controlling proper mRNA translation into protein. To explore RNA profile changes in early mouse embryos caused by Znhit3 ablation, single Znhit3-/- or control embryos were collected at different developmental stages for RNA-seq analysis.