biostudies-literatureUnknownLow TCHNIGMS NIH HHSPost-transcriptional regulation is particularly prominent during the maternal-to-zygotic transition (MZT), a developmental phase during which a large proportion of maternally provided mRNAs is repressed and cleared from metazoan embryos. RNA-binding proteins (RBPs) are key components of the post-transcriptional regulatory machinery. We show that the ORB2 RBP, the Drosophila ortholog of human Cytoplasmic Polyadenylation Element Binding Protein (hCPEB) 2-4 protein subfamily, binds to hundreds of maternally provided, rare-codon-enriched mRNAs in early embryos; that ORB2 targets are translationally repressed and unstable during the MZT; identify a U-rich motif enriched in ORB2 targets' 3'UTRs; and show that this motif confers ORB2 binding and repression to a luciferase reporter mRNA in S2 tissbioRxiv : the preprint server for biology2025.07.10.664187https://www.ebi.ac.uk/biostudies/studies/S-EPMC12265677biostudies-literatureThe ORB2 RNA-binding protein negatively regulates its target transcripts during the Drosophila maternal-to-zygotic transition via its functionally conserved Zinc-binding 'ZZ' domain.PMC12265677R01 GM129325Weerasooriya CLin SLuo HSmibert CALow TCHWang ZKaraiskakis AAngers SLipshitz HDfalseThe ORB2 RNA-binding protein negatively regulates its target transcripts during the Drosophila maternal-to-zygotic transition via its functionally conserved Zinc-binding 'ZZ' domain.Post-transcriptional regulation is particularly prominent during the maternal-to-zygotic transition (MZT), a developmental phase during which a large proportion of maternally provided mRNAs is repressed and cleared from metazoan embryos. RNA-binding proteins (RBPs) are key components of the post-transcriptional regulatory machinery. We show that the ORB2 RBP, the Drosophila ortholog of human Cytoplasmic Polyadenylation Element Binding Protein (hCPEB) 2-4 protein subfamily, binds to hundreds of maternally provided, rare-codon-enriched mRNAs in early embryos; that ORB2 targets are translationally repressed and unstable during the MZT; identify a U-rich motif enriched in ORB2 targets' 3'UTRs; and show that this motif confers ORB2 binding and repression to a luciferase reporter mRNA in S2 tiss2025-01-01T00:00:00Z2025 Oct2026-07-03T03:24:56.096Z2026-07-03T03:15:37.056ZS-EPMC122656774067222010.1101/2025.07.10.664187