C. elegans orthologs MUT-7/CeWRN-1 of Werner syndrome protein regulate neuronal plasticity

Tsung-Yuan Hsu, Bo Zhang, Noelle D. L'Etoile, Bi-Tzen Juang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Caenorhabditis elegans expresses human Werner syndrome protein (WRN)orthologs as two distinct proteins: MUT-7, with a 30' -50' exonuclease domain, and CeWRN-1, with helicase domains. How these domains cooperate remains unclear. Here, we demonstrate the different contributions of MUT-7 and CeWRN-1 to 22G small interfering RNA (siRNA) synthesis and the plasticity of neuronal signaling. MUT-7 acts specifically in the cytoplasm to promote siRNA biogenesis and in the nucleus to associate with CeWRN-1. The import of siRNA by the nuclear Argonaute NRDE-3 promotes the loading of the heterochromatin-binding protein HP1 homolog HPL-2 onto specific loci. This heterochromatin complex represses the gene expression of the guanylyl cyclase ODR-1 to direct olfactory plasticity in C. elegans. Our findings suggest that the exonuclease and helicase domains of human WRN may act in concert to promote RNA-dependent loading into a heterochromatin complex, and the failure of this entire process reduces plasticity in postmitotic neurons.

Original languageEnglish
Article number62449
Number of pages23
JournaleLife
Volume10
DOIs
StatePublished - 1 Mar 2021

Keywords

  • ODOR DISCRIMINATION
  • SYNDROME HELICASE
  • RNA INTERFERENCE
  • DNA
  • ADAPTATION
  • VISUALIZATION
  • MUTATIONS
  • OLFACTION
  • HOMOLOG
  • MUT-7

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