RRC ID 53376
Author Jannot G, Michaud P, Quévillon Huberdeau M, Morel-Berryman L, Brackbill JA, Piquet S, McJunkin K, Nakanishi K, Simard MJ.
Title GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis.
Journal PLoS Genet.
Abstract MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182, causing mRNA degradation and/or translational repression. Despite the clear conservation and molecular significance, it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal development. Using Caenorhabditis elegans to explore this question, we examined the relationship and effect on gene silencing between the GW182 orthologs, AIN-1 and AIN-2, and the microRNA-specific Argonaute, ALG-1. Homology modeling based on human Argonaute structures indicated that ALG-1 possesses conserved Tryptophan-binding Pockets required for GW182 binding. We show in vitro and in vivo that their mutations severely altered the association with AIN-1 and AIN-2. ALG-1 tryptophan-binding pockets mutant animals retained microRNA-binding and processing ability, but were deficient in reporter silencing activity. Interestingly, the ALG-1 tryptophan-binding pockets mutant phenocopied the loss of alg-1 in worms during larval stages, yet was sufficient to rescue embryonic lethality, indicating the dispensability of AINs association with the miRISC at this developmental stage. The dispensability of AINs in miRNA regulation is further demonstrated by the capacity of ALG-1 tryptophan-binding pockets mutant to regulate a target of the embryonic mir-35 microRNA family. Thus, our results demonstrate that the microRNA pathway can act independently of GW182 proteins during C. elegans embryogenesis.
Volume 12(12)
Pages e1006484
Published 2016-12
DOI 10.1371/journal.pgen.1006484
PMID 27935964
PMC PMC5147811
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics* Carrier Proteins / genetics* Embryonic Development / genetics* Gene Expression Regulation, Developmental Humans MicroRNAs / biosynthesis MicroRNAs / genetics* Mutation RNA Interference RNA-Binding Proteins / biosynthesis RNA-Binding Proteins / chemistry RNA-Binding Proteins / genetics* RNA-Induced Silencing Complex / genetics
IF 5.224
C.elegans tm2432