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

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-03-20 DOI:10.1038/s41467-025-58141-6

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

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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.

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二肽基肽酶DPF-3是动物体内微rna Argonaute补偿的守门人

MicroRNAs （miRNAs）是参与多种生物过程的重要调控因子。为了实现它们的基因抑制功能，它们被装载在mirna特异性的Argonautes中，形成mirna诱导的沉默复合体（miRISC）。哺乳动物和秀丽隐杆线虫拥有不止一种mirna特异性Argonautes，但它们之间的动态尚不清楚。在这里，我们报道了保守的二肽基肽酶DPF-3作为秀丽隐杆线虫mirna特异性Argonaute ALG-1的相互作用物。敲除dpf-3可增加alg1功能缺失动物的alg2水平和miRISC形成，从而补偿alg1缺失并挽救观察到的mirna相关缺陷。DPF-3可以在体外切割ALG-2 n端肽，但在体内似乎不依赖这种催化活性来调节ALG-2。本研究揭示了DPF-3在miRNA通路中的重要性，并为多种miRNA Argonautes如何在动物中实现适当的miRNA介导的基因调控提供了见解。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.