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

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

Molecular cell 2021 Feb 04

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Eukaryotic cells regulate 5'-triphosphorylated RNAs (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 PIR-1 (phosphatase that interacts with RNA and ribonucleoprotein particle 1) 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 RNA-dependent RNA polymerases (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 Dicer-independent Argonaute pathways and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Daniel A Chaves, Hui Dai, Lichao Li, James J Moresco, Myung Eun Oh, Darryl Conte, John R Yates, Craig C Mello, Weifeng Gu. The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans. Molecular cell. 2021 Feb 04;81(3):546-557.e5