The ORB2 RNA-binding protein negatively regulates its target transcripts during the Drosophila maternal-to-zygotic transition via its functionally conserved Zinc-binding "ZZ" domain.
Posttranscriptional 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 posttrans...
| Publicado en: | Genetics Vol. 232; no. 2; pp. 1 - 23 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Feb2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191385413&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191385413 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00166731 GNT jtl: Genetics issn: 00166731 maglogo: N pubinfo: dt: Feb2026 vid: 232 iid: 2 pid: 622 pub: Oxford University Press / USA artinfo: ui: 191385413 191385413 191385413 10.1093/genetics/iyaf241 191385413 ppf: 1 ppct: 22 formats: tig: atl: The ORB2 RNA-binding protein negatively regulates its target transcripts during the Drosophila maternal-to-zygotic transition via its functionally conserved Zinc-binding "ZZ" domain. aug: au: Low, Timothy C H Luo, Hua Weerasooriya, Chalini Wang, Zhuyi Lin, Sichun Karaiskakis, Angelo Angers, Stephane Smibert, Craig A Lipshitz, Howard D affil: Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, Ontario M5G 1M1, Canada sug: subj: RNA-Binding Proteins Metabolism Zygote Metabolism Embryo Metabolism Genes Transcription Factors Metabolism Biochemical Phenomena Animal Studies Models, Biological Flies RNA, Messenger Funding Source Precipitin Tests Mass Spectrometry Sequence Analysis Descriptive Statistics Wilcoxon Rank Sum Test Fisher's Exact Test Wilcoxon Signed Rank Test Kruskal-Wallis Test Blotting, Western ab: Posttranscriptional 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 posttranscriptional regulatory machinery. We show that the ORB2 RBP, the Drosophila ortholog of the human cytoplasmic polyadenylation element binding protein (hCPEB) 2–4 protein subfamily, binds to hundreds of maternally provided, rare-codon-enriched mRNAs in early embryos and that ORB2 targets are translationally repressed and unstable during the MZT. We identify a U-rich motif enriched in ORB2 targets' 3ʹUTRs and show that this motif confers ORB2 binding and repression to a luciferase reporter mRNA in S2 tissue culture cells. When tethered to a luciferase reporter, ORB2 and hCPEB2 (but not ORB and hCPEB1) repress translation and the C-terminal Zinc-binding ("ZZ") domain of ORB2 is necessary and sufficient for repression. ORB2 interacts with a suite of posttranscriptional regulators in early embryos; a subset of these interactions is lost upon deletion of the ZZ domain, notably with the Cup repressive complex. ORB2 targets significantly overlap with those previously identified for the repressive RBP, Smaug (SMG). Analysis of the early embryo's translatome in the presence or absence of the endogenous ZZ domain shows that mRNAs bound by ORB2 but not by SMG move onto polysomes upon ZZ domain deletion, whereas cobound transcripts do not, consistent with coregulation of the latter set of transcripts by both RBPs. Our results assign a function to the ZZ domain and position ORB2 in the posttranscriptional network that regulates maternal transcripts during the Drosophila MZT. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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