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

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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.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Tsung-Yuan Hsu

Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

Competing interests
The authors declare that no competing interests exist.
Bo Zhang

Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Noelle D L'Etoile

Department of Cell & Tissue Biology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Bi-Tzen Juang

Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

For correspondence
btjuang@nctu.edu.tw

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1210-0992

Funding

Ministry of Science and Technology, Taiwan (103-2311-B-009 -003-MY2)

Bi-Tzen Juang

Ministry of Science and Technology, Taiwan (105-2311-B-009 -002-MY3)

Bi-Tzen Juang

National Institutes of Health (2R01DC005991)

Noelle D L'Etoile

National Institutes of Health (R01DC015758)

Noelle D L'Etoile

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.