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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)546-557.e5
JournalMolecular cell
Volume81
Issue number3
DOIs
StatePublished - Feb 4 2021

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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