PAN2 Maintains mRNA Poly(A) Tail Homeostasis and Regulates RNA Degradation During Early Embryonic Development in Mice [PAIso-seq]
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ABSTRACT: RNA homeostasis regulators and surveillance factors function in the global transcriptome of oocytes and early embryos. Among them, the CNOT6L and CNOT7 proteins of the BTG4, PABPN1L, and CCR4-NOT subunits, as well as TUTs, are involved in the degradation of maternal mRNA, and are crucial for oocyte maturation and early embryonic development. However, the physiological functions of the PAN2-PAN3 complex, which is upstream of CCR4-NOT, in female reproductive cells have not yet been clarified. In this study, we have found that the absence of maternal Pan2 leads to embryonic developmental disorders and a significant decline in female reproductive capacity. By applying PAIso-seq2 and mass spectrometry analysis, we investigated the distribution and dynamics of mRNA poly(A) tails during early embryonic development. We found that the absence of Pan2 in early embryos perturbed the global balance of poly(A) tails, which in turn disrupted the transcriptome, affected mRNA degradation, and led to the accumulation of aberrant proteins. Furthermore, the maternal mRNA degradation mediated by PAN2 is crucial for the normal initiation of ZGA, and it can also regulate the expression of factors that determine cell fate in early mouse embryos. These findings highlight the crucial physiological role of PAN2 in early embryos and expand our understanding of the relationship between RNA homeostasis and the poly(A) tail.
ORGANISM(S): Mus musculus
PROVIDER: GSE308206 | GEO | 2026/07/16
REPOSITORIES: GEO
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