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Updated: May 21, 2025

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Dipeptidyl peptidase DPF-3 is a gatekeeper of microRNA Argonaute compensation in animals
Louis-Mathieu Harvey1,2, Pierre-Marc Frédérick1,2, Rajani Kanth Gudipati3
1Oncology Division, CHU de Québec - Université Laval Research Center, Québec, Canada.
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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