miRNA-mediated gene silencing in Drosophila larval development involves GW182-dependent and independent mechanisms.

Autor:	Matsuura-Suzuki E; Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan.; RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama, 351-0198, Japan., Kiyokawa K; Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan.; Institute of Industrial Science, The University of Tokyo, Meguro-ku, Tokyo, 153-8505, Japan., Iwasaki S; RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama, 351-0198, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan., Tomari Y; Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan. tomari@iqb.u-tokyo.ac.jp.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan. tomari@iqb.u-tokyo.ac.jp.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2024 Dec; Vol. 43 (23), pp. 6161-6179. Date of Electronic Publication: 2024 Sep 25.
DOI:	10.1038/s44318-024-00249-4
Abstrakt:	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. Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests. Yukihide Tomari is a member of the Advisory Editorial Board of The EMBO Journal. This has no bearing on the editorial consideration of this article for publication. (© 2024. The Author(s).)
Databáze:	MEDLINE
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