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Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression
Program in Molecular Medicine Publications and Presentations
  • Anna Y. Zinovyeva, University of Massachusetts Medical School Worcester
  • Samir Bouasker, Laval University Cancer Research Centre
  • Martin J. Simard, Laval University Cancer Research Centre
  • Christopher M. Hammell, Cold Spring Harbor Laboratory
  • Victor R. Ambros, University of Massachusetts Medical School
UMMS Affiliation
Program in Molecular Medicine
Date
4-24-2014
Document Type
Article
Medical Subject Headings
Alleles; Amino Acid Sequence; Animals; Argonaute Proteins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Carrier Proteins; Conserved Sequence; Gene Expression Regulation, Developmental; MicroRNAs; Molecular Sequence Data; Mutation; Repressor Proteins; Sequence Alignment
Abstract

microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (ALG-1 and ALG-2) that together are essential for microRNA biogenesis and function. Here, we report the identification of novel antimorphic (anti) alleles of ALG-1 as suppressors of lin-28(lf) precocious developmental phenotypes. The alg-1(anti) mutations broadly impair the function of many microRNAs and cause dosage-dependent phenotypes that are more severe than the complete loss of ALG-1. ALG-1(anti) mutant proteins are competent for promoting Dicer cleavage of microRNA precursors and for associating with and stabilizing microRNAs. However, our results suggest that ALG-1(anti) proteins may sequester microRNAs in immature and functionally deficient microRNA Induced Silencing Complexes (miRISCs), and hence compete with ALG-2 for access to functional microRNAs. Immunoprecipitation experiments show that ALG-1(anti) proteins display an increased association with Dicer and a decreased association with AIN-1/GW182. These findings suggest that alg-1(anti) mutations impair the ability of ALG-1 miRISC to execute a transition from Dicer-associated microRNA processing to AIN-1/GW182 associated effector function, and indicate an active role for ALG/Argonaute in mediating this transition.

Rights and Permissions
Citation: PLoS Genet. 2014 Apr 24;10(4):e1004286. doi: 10.1371/journal.pgen.1004286. eCollection 2014. Link to article on publisher's site
Comments

Copyright: © 2014 Zinovyeva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources
Link to Article in PubMed
Keywords
  • MicroRNAs,
  • Phenotypes,
  • Alleles,
  • Mutation,
  • RNA extraction,
  • Immunoprecipitation,
  • Larvae,
  • Biosynthesis
PubMed ID
24763381
Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Anna Y. Zinovyeva, Samir Bouasker, Martin J. Simard, Christopher M. Hammell, et al.. "Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression" Vol. 10 Iss. 4 (2014) ISSN: 1553-7390 (Linking)
Available at: http://works.bepress.com/victor_ambros/26/