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The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans

By Daniel A Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte, John R. Yates, Craig C Mello, Weifeng Gu

Posted 04 Aug 2020
bioRxiv DOI: 10.1101/2020.08.03.235143

Eukaryotic cells regulate 5’ triphosphorylated (ppp-) RNAs to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR1 family of RNA polyphosphatases remove both the β and γ phosphates from ppp-RNAs. Here we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RdRPs and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in both somatic and germline development. Our findings suggest that PIR-1 modulates both Dicer-dependent and - independent Argonaute pathways, and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species. ### Competing Interest Statement The authors have declared no competing interest.

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