title: A continuum of mRNP complexes in embryonic microRNA-mediated silencing.
abstract: MicroRNAs (miRNAs) impinge on the translation and stability of their target mRNAs, and play key roles in development, homeostasis and disease. The gene regulation mechanisms they instigate are largely mediated through the CCR4–NOT deadenylase complex, but the molecular events that occur on target mRNAs are poorly resolved. We observed a broad convergence of interactions of germ granule and P body mRNP components on AIN-1/GW182 and NTL-1/CNOT1 in Caenorhabditis elegans embryos. We show that the miRISC progressively matures on the target mRNA from a scanning form into an effector mRNP particle by sequentially recruiting the CCR4–NOT complex, decapping and decay, or germ granule proteins. Finally, we implicate intrinsically disordered proteins, key components in mRNP architectures, in the embryonic function of lsy-6 miRNA. Our findings define dynamic steps of effector mRNP assembly in miRNA-mediated silencing, and identify a functional continuum between germ granules and P bodies in the C. elegans embryo.
authors.forename: Edlyn
authors.initials: E
authors.lastname: Wu
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3G 1Y6 Canada.
authors.forename: Clément
authors.initials: C
authors.lastname: Chapat
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3G 1Y6 Canada.
authors.forename: Mathieu N
authors.initials: MN
authors.lastname: Flamand
authors.affiliation: Department of Developmental Biology and Cancer Research, The Institute For Medical Research-Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cohen
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
authors.forename: Mihail
authors.initials: M
authors.lastname: Sarov
authors.affiliation: Department of Developmental Biology and Cancer Research, The Institute For Medical Research-Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Tabach
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3G 1Y6 Canada.
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Duchaine
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; D064267:Intrinsically Disordered Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; D012261:Ribonucleoproteins; C491329:cog-1 protein, C elegans; C026452:messenger ribonucleoprotein; D012260:Ribonucleases; C445084:mRNA deadenylase