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Shirayama, Masaki; Seth, Meetu; Lee, Heng-Chi; Gu, Weifeng; Ishidate, Takao; Conte, Darryl; Mello, Craig C.
Cell, 07/2012, Letnik: 150, Številka: 1Journal Article
Organisms employ a fascinating array of strategies to silence invasive nucleic acids such as transposons and viruses. Although evidence exists for several pathways that detect foreign sequences, including pathways that sense copy number, unpaired DNA, or aberrant RNA (e.g., dsRNA), in many cases, the mechanisms used to distinguish “self” from “nonself” nucleic acids remain mysterious. Here, we describe an RNA-induced epigenetic silencing pathway that permanently silences single-copy transgenes. We show that the Piwi Argonaute PRG-1 and its genomically encoded piRNA cofactors initiate permanent silencing, and maintenance depends on chromatin factors and the WAGO Argonaute pathway. Our findings support a model in which PRG-1 scans for foreign sequences and two other Argonaute pathways serve as epigenetic memories of “self” and “nonself” RNAs. These findings suggest how organisms can utilize RNAi-related mechanisms to detect foreign sequences not by any molecular signature, but by comparing the foreign sequence to a memory of previous gene expression. Display omitted ► Epigenetic silencing triggered by piRNA-mediated recognition of nonself RNA ► piRNAs scan using imperfect base pairing to initiate gene silencing ► Maintenance of silencing requires chromatin factors and RdRP-generated small RNAs ► Activating and silencing signals may compete in self versus nonself discrimination Evidence for a provocative theory that places piRNAs at the center of a “self” versus “nonself” sensor, with some piRNAs functioning to silence foreign DNA and others as part of a mechanism that protects endogenous germline-expressed genes from aberrant silencing.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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