RRC ID 65380
Author Hsu TY, Zhang B, L'Etoile ND, Juang BT.
Title C. elegans orthologs MUT-7/CeWRN-1 of Werner syndrome protein regulate neuronal plasticity.
Journal Elife
Abstract Caenorhabditis elegans expresses human Werner syndrome protein (WRN) orthologs as two distinct proteins: MUT-7, with a 3'-5' 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.
Volume 10
Published 2021-3-1
DOI 10.7554/eLife.62449
PII 62449
PMID 33646120
PMC PMC7946423
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / metabolism DNA Helicases / genetics DNA Helicases / metabolism* Exonucleases Heterochromatin Neuronal Plasticity RNA, Small Interfering / metabolism Werner Syndrome / genetics Werner Syndrome / metabolism* Werner Syndrome Helicase / genetics Werner Syndrome Helicase / metabolism*
C.elegans tm1489