title: POS-1 and GLD-1 repress glp-1 translation through a conserved binding-site cluster.
abstract: RNA-binding proteins (RBPs) coordinate cell fate specification and differentiation in a variety of systems. RNA regulation is critical during oocyte development and early embryogenesis, in which RBPs control expression from maternal mRNAs encoding key cell fate determinants. The Caenorhabditis elegans Notch homologue glp-1 coordinates germline progenitor cell proliferation and anterior fate specification in embryos. A network of sequence-specific RBPs is required to pattern GLP-1 translation. Here, we map the cis-regulatory elements that guide glp-1 regulation by the CCCH-type tandem zinc finger protein POS-1 and the STAR-domain protein GLD-1. Our results demonstrate that both proteins recognize the glp-1 3' untranslated region (UTR) through adjacent, overlapping binding sites and that POS-1 binding excludes GLD-1 binding. Both factors are required to repress glp-1 translation in the embryo, suggesting that they function in parallel regulatory pathways. It is intriguing that two equivalent POS-1-binding sites are present in the glp-1 3' UTR, but only one, which overlaps with a translational derepression element, is functional in vivo. We propose that POS-1 regulates glp-1 mRNA translation by blocking access of other RBPs to a key regulatory sequence.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Farley
authors.forename: Sean P
authors.initials: SP
authors.lastname: Ryder
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000254:growth & development; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics; D016601:RNA-Binding Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020506:Untranslated Regions / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C094448:GLD-1 protein, C elegans; C117258:POS-1 protein, C elegans; D016601:RNA-Binding Proteins; D020506:Untranslated Regions; D052216:Glucagon-Like Peptide 1