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二肽基肽酶DPF-3是动物体内微小RNA Argonaute补偿的守门人。

Dipeptidyl peptidase DPF-3 is a gatekeeper of microRNA Argonaute compensation in animals.

作者信息

Harvey Louis-Mathieu, Frédérick Pierre-Marc, Gudipati Rajani Kanth, Michaud Pascale, Houle François, Young Daniel, Desbiens Catherine, Ladouceur Shanna, Dufour Antoine, Großhans Helge, Simard Martin J

机构信息

Oncology Division, CHU de Québec - Université Laval Research Center, Québec, Canada.

Université Laval Cancer Research Centre, Québec, Canada.

出版信息

Nat Commun. 2025 Mar 20;16(1):2738. doi: 10.1038/s41467-025-58141-6.

DOI:10.1038/s41467-025-58141-6
PMID:40108168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11923051/
Abstract

MicroRNAs (miRNAs) are essential regulators involved in multiple biological processes. To achieve their gene repression function, they are loaded in miRNA-specific Argonautes to form the miRNA-induced silencing complex (miRISC). Mammals and C. elegans possess more than one paralog of miRNA-specific Argonautes, but the dynamic between them remains unclear. Here, we report the conserved dipeptidyl peptidase DPF-3 as an interactor of the miRNA-specific Argonaute ALG-1 in C. elegans. Knockout of dpf-3 increases ALG-2 levels and miRISC formation in alg-1 loss-of-function animals, thereby compensating for ALG-1 loss and rescuing miRNA-related defects observed. DPF-3 can cleave an ALG-2 N-terminal peptide in vitro but does not appear to rely on this catalytic activity to regulate ALG-2 in vivo. This study uncovers the importance of DPF-3 in the miRNA pathway and provides insights into how multiple miRNA Argonautes contribute to achieving proper miRNA-mediated gene regulation in animals.

摘要

微小RNA（miRNA）是参与多种生物学过程的重要调节因子。为实现其基因抑制功能，它们被装载到miRNA特异性的AGO蛋白中，形成miRNA诱导沉默复合体（miRISC）。哺乳动物和秀丽隐杆线虫拥有不止一种miRNA特异性AGO蛋白的旁系同源物，但它们之间的动态关系仍不清楚。在这里，我们报道保守的二肽基肽酶DPF-3是秀丽隐杆线虫中miRNA特异性AGO蛋白ALG-1的相互作用蛋白。敲除dpf-3可增加功能缺失的alg-1动物中ALG-2的水平和miRISC的形成，从而补偿ALG-1的缺失并挽救观察到的与miRNA相关的缺陷。DPF-3可以在体外切割ALG-2的N端肽段，但在体内似乎并不依赖这种催化活性来调节ALG-2。这项研究揭示了DPF-3在miRNA途径中的重要性，并为多种miRNA AGO蛋白如何在动物中实现适当的miRNA介导的基因调控提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/3a8ccc075d08/41467_2025_58141_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/ae332ab3c7f9/41467_2025_58141_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/23811101284d/41467_2025_58141_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/b45b1f3ea134/41467_2025_58141_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/46484a4e2ebd/41467_2025_58141_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/926f1fa48f10/41467_2025_58141_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/ad073f365ba5/41467_2025_58141_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/3a8ccc075d08/41467_2025_58141_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/ae332ab3c7f9/41467_2025_58141_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/23811101284d/41467_2025_58141_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/b45b1f3ea134/41467_2025_58141_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/46484a4e2ebd/41467_2025_58141_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/926f1fa48f10/41467_2025_58141_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/ad073f365ba5/41467_2025_58141_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1162/11923051/3a8ccc075d08/41467_2025_58141_Fig7_HTML.jpg

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