| Autor: |
Wyatt CDR; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Pernaute B; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Gohr A; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Miret-Cuesta M; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Goyeneche L; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Rovira Q; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Salzer MC; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Boke E; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Bogdanovic O; Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2010, Australia., Bonnal S; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain., Irimia M; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; ICREA, Barcelona, Spain. |
| Abstrakt: |
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 zygotes reduces the levels of exon skipping at ZGA and leads to increased p53-mediated DNA damage response. We propose that mammalian embryos undergo an evolutionarily conserved, developmentally programmed splicing failure at ZGA that contributes to the attenuation of cellular responses to DNA damage. |
