RRC ID 80829
Author Chen S, Phillips CM.
Title HRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1.
Journal Nat Commun
Abstract 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 Argonaute HRDE-1 in its small RNA unbound state. In the absence of HRDE-2, HRDE-1 exclusively loads CSR-class 22G-RNAs rather than WAGO-class 22G-RNAs, resulting in inappropriate H3K9me3 deposition on CSR-target genes. Thus, our study demonstrates that the recruitment of unloaded HRDE-1 to germ granules, mediated by HRDE-2, is critical to ensure that the correct small RNAs are used to guide nuclear RNA silencing in the C. elegans germline.
Volume 15(1)
Pages 957
Published 2024-2-1
DOI 10.1038/s41467-024-45245-8
PII 10.1038/s41467-024-45245-8
PMID 38302462
PMC PMC10834429
MeSH Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Germ Cells / metabolism RNA Interference RNA, Small Interfering / genetics RNA, Small Interfering / metabolism
C.elegans tm1200 tm116 tm116102