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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\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    . Here, we generated\n                    <jats:italic>gw182<\/jats:italic>\n                    -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\n                    <jats:italic>gw182<\/jats:italic>\n                    -null first-instar larvae. Nevertheless,\n                    <jats:italic>gw182<\/jats:italic>\n                    -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.\n                  <\/jats:p>","DOI":"10.1038\/s44318-024-00249-4","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T16:51:09Z","timestamp":1727283069000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["miRNA-mediated gene silencing in Drosophila larval development involves GW182-dependent and independent mechanisms"],"prefix":"10.1038","volume":"43","author":[{"given":"Eriko","family":"Matsuura-Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Kiyokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-3754","authenticated-orcid":false,"given":"Shintaro","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8442-0851","authenticated-orcid":false,"given":"Yukihide","family":"Tomari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"249_CR1","doi-asserted-by":"publisher","first-page":"W537","DOI":"10.1093\/nar\/gky379","volume":"46","author":"E Afgan","year":"2018","unstructured":"Afgan E, Baker D, Batut B, van den Beek M, Bouvier D, Cech M, Chilton J, Clements D, Coraor N, Gr\u00fcning BA et al (2018) The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. 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Yukihide Tomari is a member of the Advisory Editorial Board of\n                      The EMBO Journal\n                      . This has no bearing on the editorial consideration of this article for publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}],"article-number":"19"}}