Molecular Cell
Volume 81, Issue 3, 4 February 2021, Pages 546-557.e5
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Article
The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans

https://doi.org/10.1016/j.molcel.2020.12.004Get rights and content
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Highlights

  • PIR-1 modifies triphosphorylated RNAs, generating monophosphorylated RNAs

  • PIR-1 is required for the biogenesis of 26G-RNAs in C. elegans germlines and embryos

  • 26G-RNAs are generated in a non-processive but recursive mode using mRNA templates

Summary

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.

Keywords

RNA phosphatase
RNAi
germline gene regulation
regulation of triphosphorylated RNA
spermatogenesis
embryogenesis
germline small RNAs
mRNA regulation
double-stranded RNAs
RNA binding proteins

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