RNA exosome ribonuclease DIS3 degrades Pou6f1 to promote mouse pre-implantation cell differentiation.

ABSTRACT: Mammalian development is precisely controlled by cell differentiation. Identifying new regulators and investigating their interactions provide insight into genetic networks defining pre-implantation development. We established a knockout mouse model of Dis3, an exosome associated ribonuclease. Homozygous Dis3 null embryos arrest at the morula stage of development. Using single-embryo RNA sequencing (RNA-seq), we observed persistence of Pou6f1 mRNA in homozygous null Dis3 embryos and that the cognate protein represses transcription of Nanog and Cdx2. The resultant defects in cell differentiation disrupt the morula-to-blastocyst transition and are embryonic lethal. Microinjection of Dis3 mRNA into zygotes rescues the phenotype. Point mutations of Dis3 ribonuclease in individual blastomeres p

SUBMITTER: Wu D 

PROVIDER: S-EPMC10387129 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature