A developmentally programmed splicing failure contributes to DNA damage response attenuation during mammalian zygotic genome activation.

ABSTRACT: Transition from maternal to embryonic transcriptional control is crucial for embryogenesis. However, alternative splicing regulation during this process remains understudied. Using transcriptomic data from human, mouse, and cow preimplantation development, we show that the stage of zygotic genome activation (ZGA) exhibits the highest levels of exon skipping diversity reported for any cell or tissue type. Much of this exon skipping is temporary, leads to disruptive noncanonical isoforms, and occurs in genes enriched for DNA damage response in the three species. Two core spliceosomal components, Snrpb and Snrpd2, regulate these patterns. These genes have low maternal expression at ZGA and increase sharply thereafter. Microinjection of Snrpb/d2 messenger RNA into mouse zy

SUBMITTER: Wyatt CDR 

PROVIDER: S-EPMC9007516 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature