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A continuum of mRNP complexes in embryonic microRNA-mediated silencing.
Wu, Edlyn; Vashisht, Ajay A; Chapat, Clément; Flamand, Mathieu N; Cohen, Emiliano; Sarov, Mihail; Tabach, Yuval; Sonenberg, Nahum; Wohlschlegel, James; Duchaine, Thomas F.
Affiliation
  • Vashisht AA; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
  • Chapat C; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3G 1Y6 Canada.
  • Flamand MN; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3G 1Y6 Canada.
  • Cohen E; Department of Developmental Biology and Cancer Research, The Institute For Medical Research-Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
  • Sarov M; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
  • Tabach Y; Department of Developmental Biology and Cancer Research, The Institute For Medical Research-Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
  • Sonenberg N; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, H3G 1Y6 Canada.
  • Wohlschlegel J; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Nucleic Acids Res ; 45(4): 2081-2098, 2017 02 28.
Article in En | MEDLINE | ID: mdl-28204614
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 CCR4­NOT 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 CCR4­NOT 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.
Subject(s)

Full text: 1 Database: MEDLINE Main subject: Ribonucleoproteins / Gene Expression Regulation, Developmental / MicroRNAs / RNA Interference Type of study: Prognostic_studies Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2017 Type: Article

Full text: 1 Database: MEDLINE Main subject: Ribonucleoproteins / Gene Expression Regulation, Developmental / MicroRNAs / RNA Interference Type of study: Prognostic_studies Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2017 Type: Article