AI Article Synopsis
- MicroRNAs (miRNAs) control various biological functions by silencing target genes with the help of Argonaute (AGO) proteins and the RNA-induced silencing complex (RISC).
- The scaffold protein GW182 links AGO to the CCR4-NOT complex to facilitate mRNA decay, but its role in living organisms, particularly in Drosophila melanogaster, is not well understood.
- Researchers created gw182-null flies using CRISPR/Cas9 and found that while these flies survive to the second larval stage and can still repress miRNA reporters, they show significant defects in chitin-related gene expression and tracheal development, indicating the necessity of both GW182-dependent and independent mechanisms for proper development.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612316 | PMC |
| http://dx.doi.org/10.1038/s44318-024-00249-4 | DOI Listing |
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