MassIVE MSV000092546

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Germ granule association drives small RNA specificity for a nuclear Argonaute protein

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Description

RNA interference (RNAi) is a conserved gene silencing process that exists in diverse organisms to protect genome integrity and regulate gene expression. In C. elegans, the majority of RNAi pathway proteins localize to perinuclear, phase-separated germ granules, which are comprised of sub-domains referred to as P granules, Mutator foci, Z granules, and SIMR foci. However, the protein components and function of the newly discovered SIMR foci are unknown. Here we demonstrate that HRDE-2 localizes to SIMR foci and interacts with the germline nuclear RNAi Argonaute HRDE-1. Furthermore, HRDE-1 also localizes to SIMR foci, dependent on HRDE-2, but only in its small RNA unbound state. This germ granule localization is critical to promote the small RNA binding specificity of HRDE-1 and, in the absence of HRDE-2, HRDE-1 exclusively loads CSR-class 22G-RNAs rather than WAGO-class 22G-RNAs, resulting in H3K9me3 deposition on CSR-target genes. Thus, our study demonstrates that HRDE-2 is critical to ensure that the correct small RNAs are used to guide nuclear RNA silencing in the C. elegans germline. [doi:10.25345/C55717Z5Q] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Argonaute, SIMR foci, germ granule, RNA silencing, small RNA

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Principal Investigators:
(in alphabetical order) 		Carolyn M. Phillips, University of Southern California, United States
Submitting User: adarshmayank
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