title: Regulation of maternal Wnt mRNA translation in C. elegans embryos.
abstract: The restricted spatiotemporal translation of maternal mRNAs, which is crucial for correct cell fate specification in early C. elegans embryos, is regulated primarily through the 3'UTR. Although genetic screens have identified many maternally expressed cell fate-controlling RNA-binding proteins (RBPs), their in vivo targets and the mechanism(s) by which they regulate these targets are less clear. These RBPs are translated in oocytes and localize to one or a few blastomeres in a spatially and temporally dynamic fashion unique for each protein and each blastomere. Here, we characterize the translational regulation of maternally supplied mom-2 mRNA, which encodes a Wnt ligand essential for two separate cell-cell interactions in early embryos. A GFP reporter that includes only the mom-2 3'UTR is translationally repressed properly in oocytes and early embryos, and then correctly translated only in the known Wnt signaling cells. We show that the spatiotemporal translation pattern of this reporter is regulated combinatorially by a set of nine maternally supplied RBPs. These nine proteins all directly bind the mom-2 3'UTR in vitro and function as positive or negative regulators of mom-2 translation in vivo. The net translational readout for the mom-2 3'UTR reporter is determined by competitive binding between positive- and negative-acting RBPs for the 3'UTR, along with the distinct spatiotemporal localization patterns of these regulators. We propose that the 3'UTR of maternal mRNAs contains a combinatorial code that determines the topography of associated RBPs, integrating positive and negative translational inputs.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Marieke
authors.initials: M
authors.lastname: Oldenbroek
authors.forename: Scott M
authors.initials: SM
authors.lastname: Robertson
authors.forename: Tugba
authors.initials: T
authors.lastname: Guven-Ozkan
authors.forename: Caroline
authors.initials: C
authors.lastname: Spike
authors.forename: David
authors.initials: D
authors.lastname: Greenstein
authors.forename: Rueyling
authors.initials: R
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001667:Binding, Competitive; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D034443:RNA Transport / Q000235:genetics; D023121:RNA, Messenger, Stored / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D023121:RNA, Messenger, Stored; D051153:Wnt Proteins; D049452:Green Fluorescent Proteins
keywords: 3′UTR; Caenorhabditis elegans; Wnt