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bioRxiv · 10.1101/2024.02.27.581607

Interaction between a J-domain co-chaperone and a specific Argonaute protein contributes to microRNA function in animals

Frederick, P.-M.·Jannot, G.·Banville, I.·Simard, M. J.
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Abstract

MicroRNAs (miRNAs) are essential regulators of several biological processes. They are loaded onto Argonaute (AGO) proteins to achieve their repressive function, forming the microRNA-Induced Silencing Complex (miRISC). While several AGO proteins are expressed in plants and animals, it is still unclear why specific AGOs are strictly binding miRNAs. Here, we identified the co-chaperone DNJ-12 as a new interactor of ALG-1, one of the two major miRNA-specific AGOs in Caenorhabditis elegans. DNJ-12 does not interact with ALG-2, the other major miRNA-specific AGO, and PRG-1 and RDE-1, two AGOs involved in other small RNA pathways, making it a specific actor in ALG-1-dependent miRNA-mediated gene silencing. The loss of DNJ-12 causes developmental defects associated with defective miRNA function. Using the Auxin Inducible Degron (AID) system, a powerful tool to acutely degrade proteins in specific tissues, we show that DNJ-12 depletion hampers ALG-1 interaction with HSP70, a chaperone required for miRISC loading in vitro. Moreover, DNJ-12 depletion leads to the decrease of several miRNAs and prevents their loading onto ALG-1. This study uncovers the importance of a co-chaperone for the miRNA function in vivo and provides insights to explain how different small RNAs associate with specific AGO in animals.

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Frederick, P.-M., Jannot, G., Banville, I., Simard, M. J.. 2024-02-27. Interaction between a J-domain co-chaperone and a specific Argonaute protein contributes to microRNA function in animals. https://doi.org/10.1101/2024.02.27.581607

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