title: POS-1 Promotes Endo-mesoderm Development by Inhibiting the Cytoplasmic Polyadenylation of neg-1 mRNA.
abstract: The regulation of mRNA translation is of fundamental importance in biological mechanisms ranging from embryonic axis specification to the formation of long-term memory. POS-1 is one of several CCCH zinc-finger RNA-binding proteins that regulate cell fate specification during C. elegans embryogenesis. Paradoxically, pos-1 mutants exhibit striking defects in endo-mesoderm development but have wild-type distributions of SKN-1, a key determinant of endo-mesoderm fates. RNAi screens for pos-1 suppressors identified genes encoding the cytoplasmic poly(A)-polymerase homolog GLD-2, the Bicaudal-C homolog GLD-3, and the protein NEG-1. We show that NEG-1 localizes in anterior nuclei, where it negatively regulates endo-mesoderm fates. In posterior cells, POS-1 binds the neg-1 3' UTR to oppose GLD-2 and GLD-3 activities that promote NEG-1 expression and cytoplasmic lengthening of the neg-1 mRNA poly(A) tail. Our findings uncover an intricate series of post-transcriptional regulatory interactions that, together, achieve precise spatial expression of endo-mesoderm fates in C. elegans embryos.
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elewa
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shirayama
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Ebru
authors.initials: E
authors.lastname: Kaymak
authors.affiliation: Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria 3800, Australia; Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative, Carlton, Victoria 3053, Australia.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Harrison
authors.affiliation: Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria 3800, Australia; Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative, Carlton, Victoria 3053, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Powell
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, Life Science and Bioengineering Center, Gateway Park, 60 Prescott Street, Worcester, MA 01605, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Chute
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Woolf
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Dongni
authors.initials: D
authors.lastname: Yi
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Ishidate
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, Life Science and Bioengineering Center, Gateway Park, 60 Prescott Street, Worcester, MA 01605, USA.
authors.forename: Jagan
authors.initials: J
authors.lastname: Srinivasan
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Traude H
authors.initials: TH
authors.lastname: Beilharz
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Ryder
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Electronic address: craig.mello@umassmed.edu.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005854:Germ Cells / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D026723:Polyadenylation / Q000502:physiology*; D018510:RNA, Helminth / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000601450:NEG-1 protein, C elegans; D009687:Nuclear Proteins; C117258:POS-1 protein, C elegans; D018510:RNA, Helminth; D012333:RNA, Messenger; D016601:RNA-Binding Proteins