A Tudor domain protein, SIMR-1, promotes siRNA production at piRNA-targeted mRNAs in C. elegans
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.
Data availability
High-throughput sequencing data for RNA-sequencing libraries generated during this study are available through Gene Expression Omnibus (GSE138220 for preliminary simr-1 small RNA, and simr-1 mRNA sequencing data, GSE134573 for mut-16 small RNA and mRNA sequencing data, and GSE145217 for prg-1 and ergo-1 small RNA sequencing data).
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A Tudor domain protein, SIMR-1, promotes siRNA production at piRNA-targeted mRNAs in C. elegansNCBI Gene Expression Omnibus, GSE138220.
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RNAi pathways repress reprogramming of C. elegans germ cells during heat stressNCBI Gene Expression Omnibus, GSE134573.
Article and author information
Author details
Funding
National Cancer Institute (K22 CA177897)
- Carolyn Marie Phillips
National Institute of General Medical Sciences (R35 GM119656)
- Carolyn Marie Phillips
National Institute of General Medical Sciences (T32 GM118289)
- Dieu An H Nguyen
National Institute of General Medical Sciences (R35 GM119775)
- Taiowa A Montgomery
Deutsche Forschungsgemeinschaft (KE1888/1-1)
- Rene F Ketting
Deutsche Forschungsgemeinschaft (KE1888/1-2)
- Rene F Ketting
Pew Charitable Trusts (Pew Scholar in the Biomedical Sciences)
- Carolyn Marie Phillips
National Science Foundation (DGE 1418060)
- Celja J Uebel
University of Southern California (Dornsife College Chemistry-Biology Interface trainee)
- Celja J Uebel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
Version history
- Received: March 8, 2020
- Accepted: April 24, 2020
- Accepted Manuscript published: April 27, 2020 (version 1)
- Version of Record published: May 28, 2020 (version 2)
Copyright
© 2020, Manage et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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