CSR-1 mediates RNA activation, RNAa, a self-RNA recognition pathway that promotes gene expression in the C. elegans germline

ABSTRACT: 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

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Craig Mello 

PROVIDER: E-GEOD-49532 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress