C. elegans orthologs MUT-7/CeWRN-1 of Werner syndrome protein regulate neuronal plasticity
| Autor: | Noelle D. L'Etoile, Bo Zhang, Tsung-Yuan Hsu, Bi-Tzen Juang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Exonuclease Small interfering RNA congenital hereditary and neonatal diseases and abnormalities Heterochromatin QH301-705.5 Science General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine RNA interference neuronal plasticity 3'-5' exonuclease Biology (General) Caenorhabditis elegans 22G small RNA General Immunology and Microbiology biology General Neuroscience Helicase General Medicine Argonaute biology.organism_classification Cell biology werner syndrome protein 030104 developmental biology C. elegans biology.protein Medicine Heterochromatin protein 1 030217 neurology & neurosurgery Research Article Neuroscience |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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