title: Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing.
abstract: An animal that can transfer gene-regulatory information from somatic cells to germ cells may be able to communicate changes in the soma from one generation to the next. In the worm Caenorhabditis elegans, expression of double-stranded RNA (dsRNA) in neurons can result in the export of dsRNA-derived mobile RNAs to other distant cells. Here, we show that neuronal mobile RNAs can cause transgenerational silencing of a gene of matching sequence in germ cells. Consistent with neuronal mobile RNAs being forms of dsRNA, silencing of target genes that are expressed either in somatic cells or in the germline requires the dsRNA-selective importer SID-1. In contrast to silencing in somatic cells, which requires dsRNA expression in each generation, silencing in the germline is heritable after a single generation of exposure to neuronal mobile RNAs. Although initiation of inherited silencing within the germline requires SID-1, a primary Argonaute RDE-1, a secondary Argonaute HRDE-1, and an RNase D homolog MUT-7, maintenance of inherited silencing is independent of SID-1 and RDE-1, but requires HRDE-1 and MUT-7. Inherited silencing can persist for >25 generations in the absence of the ancestral source of neuronal dsRNA. Therefore, our results suggest that sequence-specific regulatory information in the form of dsRNA can be transferred from neurons to the germline to cause transgenerational silencing.
authors: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors: Sindhuja
authors: S
authors: Devanapally
authors: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors: Snusha
authors: S
authors: Ravikumar
authors: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 amjose@umd.edu.
authors: Antony M
authors: AM
authors: Jose
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D020868:Gene Silencing; D005854:Germ Cells; D009474:Neurons / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics*
chemical_list: D012330:RNA, Double-Stranded
keywords: Weismann barrier; epigenetics; mobile RNAs; soma to germline
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