Abstract
piRNAs play a critical role in the regulation of transposons and other germline genes. In Caenorhabditis elegans, regulation of piRNA target genes is mediated by the mutator 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 mutator complex are unknown. Here, we identify the Tudor domain protein, SIMR-1, as acting downstream of piRNA production and upstream of mutator complex-dependent siRNA biogenesis. Interestingly, SIMR-1 also localizes to distinct subcellular foci adjacent to P granules and Mutator foci, two phase-separated condensates that are the sites of piRNA-dependent mRNA recognition and mutator 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 mutator complex.
Highlights
IntroductionSmall RNAs, ranging from ~18–30 nucleotides in length, regulate cellular mRNAs through sequence complementarity
In many eukaryotes, small RNAs, ranging from ~18–30 nucleotides in length, regulate cellular mRNAs through sequence complementarity
RSD-2 is a small RNA factor required for exogenous RNAi introduced at low doses and not previously known to interact with the mutator complex (Sakaguchi et al, 2014; Han et al, 2008; Tijsterman et al, 2004; Zhang et al, 2012); WAGO-1 is an Argonaute protein that localizes to P granules but was found to interact with MUT-16 in a yeast two-hybrid screen (Supplementary file 1; Gu et al, 2009; Phillips et al, 2014); A
Summary
Small RNAs, ranging from ~18–30 nucleotides in length, regulate cellular mRNAs through sequence complementarity. Argonaute proteins are key mediators of RNA silencing; by binding to small RNAs, which interact with fully or partially complementary mRNAs, the Argonaute proteins can promote transcription repression, translation inhibition, and RNA decay of targeted mRNAs (Hutvagner and Simard, 2008; Claycomb, 2014). Through this regulation of both endogenous and foreign RNAs, small RNAs play key roles in maintaining proper gene expression and silencing deleterious RNAs (Claycomb, 2014; Ketting, 2011). In C. elegans, a small RNA amplification pathway dependent on the mutator complex, which includes an RNA-dependent
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