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. 2014 Mar 1;28(5):423–431. doi: 10.1101/gad.236414.113

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© 2014 Stuwe et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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Figure 5. — Three small RNA pathways cooperate to repress nonself sequences in C. elegans. The expression of a gene (blue) in the germline leads to generation of complementary 22G-RNAs by an RNA-dependent RNA polymerase (RdRP). 22G-RNAs associated with the CSR-1 protein are transmitted to the next generation through the female germline. PRG-1 guided by 21U-RNAs has a potential to recognize and repress any sequence; however, transcripts targeted by the transgenerationally inherited CSR-1/22G-RNA complex are excluded from this repression. Accordingly, only newly expressed nonself sequences (red) are recognized for repression by 21U-RNAs and PRG-1. Recognition of a sequence by PRG-1 causes generation of 22G-RNAs by an RdRP, and these 22G-RNAs associate with the nuclear WAGO-9 protein. The recognition of nascent transcripts by WAGO-9/22G-RNAs leads to deposition of the H3K9me3 mark on the target and its transcriptional silencing. WAGO-9 and the associated 22G-RNAs are transmitted to the next generation, ensuring a memory of nonself sequences that have to be repressed.