A tudor domain protein, SIMR-1, promotes siRNA production at piRNA-targeted mRNAs in <i>C. elegans</i>.

Manage, Kevin I; Rogers, Alicia K; Wallis, Dylan C; Uebel, Celja J; Anderson, Dorian C; Nguyen, Dieu An H; Arca, Katerina; Brown, Kristen C et al. · Elife · 2020

basic_science · Level V

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Abstract

piRNAs play a critical role in the regulation of transposons and other germline genes. In <i>Caenorhabditis elegans</i>, regulation of piRNA target genes is mediated by the <i>mutator</i> complex, which synthesizes high levels of siRNAs through the activity of an RNA-dependent RNA polymerase. However, the steps between mRNA recognition by the piRNA pathway and siRNA amplification by the <i>mutator</i> complex are unknown. Here, we identify the Tudor domain protein, SIMR-1, as acting downstream of piRNA production and upstream of <i>mutator</i> complex-dependent siRNA biogenesis. Interestingly, SIMR-1 also localizes to distinct subcellular foci adjacent to P granules and <i>Mutator</i> foci, two phase-separated condensates that are the sites of piRNA-dependent mRNA recognition and <i>mutator</i> complex-dependent siRNA amplification, respectively. Thus, our data suggests a role for multiple perinuclear condensates in organizing the piRNA pathway and promoting mRNA regulation by the <i>mutator</i> complex.

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