Cargando…
Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression
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 th...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998888/ https://www.ncbi.nlm.nih.gov/pubmed/24763381 http://dx.doi.org/10.1371/journal.pgen.1004286 |
_version_ | 1782313429882634240 |
---|---|
author | Zinovyeva, Anna Y. Bouasker, Samir Simard, Martin J. Hammell, Christopher M. Ambros, Victor |
author_facet | Zinovyeva, Anna Y. Bouasker, Samir Simard, Martin J. Hammell, Christopher M. Ambros, Victor |
author_sort | Zinovyeva, Anna Y. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3998888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39988882014-04-29 Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression Zinovyeva, Anna Y. Bouasker, Samir Simard, Martin J. Hammell, Christopher M. Ambros, Victor PLoS Genet Research Article 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. Public Library of Science 2014-04-24 /pmc/articles/PMC3998888/ /pubmed/24763381 http://dx.doi.org/10.1371/journal.pgen.1004286 Text en © 2014 Zinovyeva et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Zinovyeva, Anna Y. Bouasker, Samir Simard, Martin J. Hammell, Christopher M. Ambros, Victor Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression |
title | Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression |
title_full | Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression |
title_fullStr | Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression |
title_full_unstemmed | Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression |
title_short | Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression |
title_sort | mutations in conserved residues of the c. elegans microrna argonaute alg-1 identify separable functions in alg-1 mirisc loading and target repression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998888/ https://www.ncbi.nlm.nih.gov/pubmed/24763381 http://dx.doi.org/10.1371/journal.pgen.1004286 |
work_keys_str_mv | AT zinovyevaannay mutationsinconservedresiduesofthecelegansmicrornaargonautealg1identifyseparablefunctionsinalg1miriscloadingandtargetrepression AT bouaskersamir mutationsinconservedresiduesofthecelegansmicrornaargonautealg1identifyseparablefunctionsinalg1miriscloadingandtargetrepression AT simardmartinj mutationsinconservedresiduesofthecelegansmicrornaargonautealg1identifyseparablefunctionsinalg1miriscloadingandtargetrepression AT hammellchristopherm mutationsinconservedresiduesofthecelegansmicrornaargonautealg1identifyseparablefunctionsinalg1miriscloadingandtargetrepression AT ambrosvictor mutationsinconservedresiduesofthecelegansmicrornaargonautealg1identifyseparablefunctionsinalg1miriscloadingandtargetrepression |