Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

PiRNAs initiate an epigenetic memory of non-self RNA in the C. elegans germline.

ABSTRACT: Organisms exhibit a fascinating array of gene-silencing pathways, which have evolved in part, to confront invasive nucleic acids such as transposons and viruses. A key question raised by the existence of these pathways is how do they distinguish M-bM-^@M-^\selfM-bM-^@M-^] from M-bM-^@M-^\non-selfM-bM-^@M-^] nucleic acids? Evidence exists for a number of mechanisms that might facilitate detection of foreign sequences including mechanisms that sense copy-number, unpaired DNA, or aberrant RNA (e.g.dsRNA). Here we describe an RNA-induced epigenetic silencing pathway, RNAe, that permanently silences single-copy transgenes. We show that the Piwi Argonaute PRG-1 and its genomically encoded piRNA cofactors initiate RNAe, while maintenance depends on chromatin factors and the WAGO Argonaute pathway. Our findings support a model in which PRG-1 scans for foreign sequences, while two other Argonaute pathways serve as epigenetic memories of "self" and "non-self" RNAs. These findings suggest how organisms may utilize RNAi-related mechanisms not only to recognize and silence foreign genes, but also to keep inventory of all genes expressed in the germ-line. Examine small RNA population changes in different transgene lines. FLAG::WAGO-9 was immunoprecipitated from 20 mg of lysate essentially as described (Gu et al., 2009). Small RNAs were extracted from WAGO-9 immune complexes as well as a portion of the input lysate, gel-purified, pre-treated with TAP, cloned and sequenced as described (Gu et al., 2009).

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Weifeng Gu

PROVIDER: E-GEOD-38724 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline.

Shirayama Masaki M Seth Meetu M Lee Heng-Chi HC Gu Weifeng W Ishidate Takao T Conte Darryl D Mello Craig C CC

Cell 20120625 1

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. ...[more]

PMID: 22738726

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Project description:Epigenetic inheritance is the transmission of information independently of the nucleotide sequence of the genome. A fundamental question in biology is to what extent does epigenetics contribute to trans-generational inheritance. Here we investigate the role of Argonaute-small-RNA pathways in epigenetic inheritance in the nematode C. elegans. Argonautes present their guide RNAs for base-pairing with target sequences and, upon binding, can cleave the target RNA and/or recruit cofactors that mediate post-transcriptional or transcriptional silencing 1,2. Previous studies have shown that Argonaute small-RNA pathways reinforce and maintain epigenetic silencing in C. elegans 3-5. For example, the conserved PIWI-related Argonaute PRG-1 initiates a remarkably stable mode of epigenetic silencing, termed RNA-induced epigenetic silencing (RNAe) 3. Alleles that are silenced by RNAe send trans-acting Argonaute-small-RNA signals that can act in a sequence-specific manner to induce the permanent Epigenetic inheritance is the transmission of information independently of the nucleotide sequence of the genome. A fundamental question in biology is to what extent does epigenetics contribute to trans-generational inheritance. Here we investigate the role of Argonaute-small-RNA pathways in epigenetic inheritance in the nematode C. elegans. Argonautes present their guide RNAs for base-pairing with target sequences and, upon binding, can cleave the target RNA and/or recruit cofactors that mediate post-transcriptional or transcriptional silencing 1,2. Previous studies have shown that Argonaute small-RNA pathways reinforce and maintain epigenetic silencing in C. elegans 3-5. For example, the conserved PIWI-related Argonaute PRG-1 initiates a remarkably stable mode of epigenetic silencing, termed RNA-induced epigenetic silencing (RNAe) 3. Alleles that are silenced by RNAe send trans-acting Argonaute-small-RNA signals that can act in a sequence-specific manner to induce the permanent silencing of homologous genes 3. Here we explore an opposite phenomenon, RNA-induced gene activation (RNAa), in which an expressed gene provides a sequence-specific signal that can activate a silent homologous gene. We provide evidence that the CSR-1 Argonaute is required for this trans-activating signal. CSR-1 engages antisense small RNAs complementary to most, if not all, germline-expressed mRNAs 6,7. Moreover, we show that the ability of a foreign sequence to mediate RNAa is correlated with acquisition of CSR-1-associated small RNAs targeting the foreign sequence. Thus CSR-1 small RNAs constitute a memory of previous germline-gene expression that protects endogenous genes from epigenetic silencing. These findings reveal a remarkably sophisticated epigenetic surveillance mechanism that monitors the flow of transgenerational information ensuring that progeny express only those genes also expressed in their parents. Examine small RNA population changes in different transgene lines

Dataset Information

PiRNAs initiate an epigenetic memory of non-self RNA in the C. elegans germline.

Publications

piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline.

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