The dynamic landscape of alternative 3' UTR during mammalian preimplantation development

Alternative polyadenylation (APA) generates mRNA isoforms with distinct 3' UTR lengths, yet its role in mammalian preimplantation development remains largely unexplored. Here, we systematically delineated single-cell 3' UTR APA dynamics in human and mouse preimplantation embryos. The pronounced cell heterogeneity and developmental stage-specificity of APA patterns were uncovered. Zygotic genome activation (ZGA) genes predominantly utilized shortened 3' UTRs, indicating a potential role for 3' UTR shortening in ZGA. Integrative analyses with APAFlow and DAPAFlow revealed that N6-methyladenosine modification and its reader proteins coordinately regulate APA via APA-associated factors during ZGA. Moreover, the occurrence and expression of 3' UTR APA events are linked to miRNAs located adjacent to polyadenylation sites. Together, these findings delineate a dynamic 3' UTR APA landscape across mammalian preimplantation stages, highlighting its contribution to cellular heterogeneity and developmental regulation. Shortened 3' UTR APA may serve as a hallmark of ZGA, providing new insight into post-transcriptional regulation during preimplantation development.