A Cytoplasmic Argonaute Protein Promotes the Inheritance of RNAi

Cell Rep. 2018 May 22;23(8):2482-2494. doi: 10.1016/j.celrep.2018.04.072.

Abstract

RNAi-elicited gene silencing is heritable and can persist for multiple generations after its initial induction in C. elegans. However, the mechanism by which parental-acquired trait-specific information from RNAi is inherited by the progenies is not fully understood. Here, we identified a cytoplasmic Argonaute protein, WAGO-4, necessary for the inheritance of RNAi. WAGO-4 exhibits asymmetrical translocation to the germline during early embryogenesis, accumulates at the perinuclear foci in the germline, and is required for the inheritance of exogenous RNAi targeting both germline- and soma-expressed genes. WAGO-4 binds to 22G-RNAs and their mRNA targets. Interestingly, WAGO-4-associated endogenous 22G-RNAs target the same cohort of germline genes as CSR-1 and contain untemplated addition of uracil at the 3' ends. The poly(U) polymerase CDE-1 is required for the untemplated uridylation of 22G-RNAs and inheritance of RNAi. Therefore, we conclude that, in addition to the nuclear RNAi pathway, the cytoplasmic RNAi machinery also promotes RNAi inheritance.

Keywords: Argonaute; Nrde; RNAi; WAGO-4; inheritance.

Publication types

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

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoplasm / metabolism*
  • Gene Silencing
  • Genes, Helminth
  • Germ Cells / metabolism
  • Inheritance Patterns / genetics*
  • Open Reading Frames / genetics
  • Protein Binding
  • RNA Interference*
  • RNA, Small Interfering / metabolism
  • Uridine / metabolism

Substances

  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • RNA, Small Interfering
  • WAGO-4 protein, C elegans
  • Uridine