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

Mol Cell. 2021 Feb 4;81(3):546-557.e5. doi: 10.1016/j.molcel.2020.12.004. Epub 2020 Dec 29.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation
  • RNA / genetics
  • RNA / metabolism*
  • RNA Caps
  • RNA Processing, Post-Transcriptional*
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Spermatogenesis
  • Substrate Specificity


  • CSR-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • RNA Caps
  • RNA
  • RNA-Dependent RNA Polymerase
  • dcr-1 protein, C elegans
  • Ribonuclease III
  • Phosphoric Monoester Hydrolases