Program in Molecular Medicine
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
Biochemistry | Developmental Biology | Molecular Biology | Molecular Genetics
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.
MicroRNAs, Phenotypes, Alleles, Mutation, RNA extraction, Immunoprecipitation, Larvae, Biosynthesis
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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.
DOI of Published Version
PLoS Genet. 2014 Apr 24;10(4):e1004286. doi: 10.1371/journal.pgen.1004286. eCollection 2014. Link to article on publisher's site
Zinovyeva AY, Bouasker S, Simard MJ, Hammell CM, Ambros VR. (2014). 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. https://doi.org/10.1371/journal.pgen.1004286. Retrieved from https://escholarship.umassmed.edu/pmm_pp/21
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