RRC ID 82594
Author Matsuura-Suzuki E, Kiyokawa K, Iwasaki S, Tomari Y.
Title miRNA-mediated gene silencing in Drosophila larval development involves GW182-dependent and independent mechanisms.
Journal EMBO J
Abstract MicroRNAs (miRNAs) regulate a wide variety of biological processes by silencing their target genes. Argonaute (AGO) proteins load miRNAs to form an RNA-induced silencing complex (RISC), which mediates translational repression and/or mRNA decay of the targets. A scaffold protein called GW182 directly binds AGO and the CCR4-NOT deadenylase complex, initiating the mRNA decay reaction. Although previous studies have demonstrated the critical role of GW182 in cultured cells as well as in cell-free systems, its biological significance in living organisms remains poorly explored, especially in Drosophila melanogaster. Here, we generated gw182-null flies using the CRISPR/Cas9 system and found that, unexpectedly, they can survive until an early second-instar larval stage. Moreover, in vivo miRNA reporters can be effectively repressed in gw182-null first-instar larvae. Nevertheless, gw182-null flies have defects in the expression of chitin-related genes and the formation of the larval trachea system, preventing them from completing larval development. Our results highlight the importance of both GW182-dependent and -independent silencing mechanisms in vivo.
Volume 43(23)
Pages 6161-6179
Published 2024-12-1
DOI 10.1038/s44318-024-00249-4
PII 10.1038/s44318-024-00249-4
PMID 39322759
PMC PMC11612316
MeSH Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism CRISPR-Cas Systems Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / growth & development Drosophila melanogaster* / metabolism Gene Expression Regulation, Developmental Gene Silencing Larva* / genetics Larva* / growth & development Larva* / metabolism MicroRNAs* / genetics MicroRNAs* / metabolism RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism
IF 9.889
Resource
Drosophila DGRC#119243 DGRC#119244 DGRC#119245 DGRC#119246 DGRC#119247 DGRC#119248 DGRC#119249 DGRC#119250 DGRC#119251 DGRC#119252 DGRC#119253 DGRC#119254 DGRC#119255 DGRC#119256 DGRC#119257 DGRC#119258 DGRC#119259 DGRC#119260