ZNHIT3 Regulates Translation to Ensure Cell Lineage Differentiation in Mouse Preimplantation Development [SMARMseq]

Upon fertilization, the mouse zygotic genome is activated and maternal RNAs as well as proteins are degraded. Early developmental programs are built on proteins encoded by zygotic mouse genes that are needed to guide early cell fate commitment. The box C/D snoRNA ribonucleoprotein (snoRNP) complex is required for rRNA biogenesis, ribosome assembly and pre-mRNA splicing essential for protein translation. Zinc finger, HIT type 3 (encoded by Znhit3) is previously identified as a component in the assembly of the box C/D snoRNP complex. Using gene-edited mice, it identifies Znhit3 as an early embryonic gene whose ablation reduces protein translation and prevents mouse embryos development beyond the morula stage. The absence of ZNHIT3 leads to decreased snoRNA and rRNA abundance which causes defects of ribosomes and mRNA splicing. Microinjection of Znhit3 cRNA partially rescues the phenotype and confirms that ZNHIT3 is required for mRNA translation during preimplantation development. Overall design: To explore changes of rRNA 2'-O-methylation in mouse embryos caused by Znhit3 ablation, embryos were collected after intercross of Znhit3+/- breeders and examined with a modified Ribo-meth sequencing method.