Zinovyeva, A. Y., Bouasker, S., Simard, M. J., Hammell, C. M., Ambros, V. (April 2014) Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression. PLoS Genetics, 10 (4). e1004286. ISSN 1553-7404 (Electronic)1553-7390 (Linking)
Preview |
PDF (Paper)
Hammell PLoS Genetics 2014b.pdf - Published Version Download (10MB) | Preview |
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.
| Item Type: | Paper |
|---|---|
| Subjects: | organism description > animal > C elegans bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Cancer Genetics CSHL Cancer Center Shared Resources > Bioinformatics Service CSHL labs > Hammell C. lab CSHL Cancer Center Shared Resources > DNA Sequencing Service |
| Depositing User: | Matt Covey |
| Date: | 24 April 2014 |
| Date Deposited: | 19 Dec 2014 17:39 |
| Last Modified: | 05 Nov 2015 15:53 |
| PMCID: | PMC3998888 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30974 |
Actions (login required)
 |
Administrator's edit/view item |