piRNAs and piRNA-Dependent siRNAs Protect Conserved and Essential C. elegans Genes from Misrouting into the RNAi Pathway

Phillips, Carolyn M.; Brown, Kristen C.; Montgomery, Brooke E. E.; Ruvkun, Gary; Montgomery, Taiowa A.

doi:10.1016/j.devcel.2015.07.009

Cited by 84 publications

(103 citation statements)

References 29 publications

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“…Indeed, in absence of HRDE-1, this silencing is no longer observed ( Figure 4C). In fact, the sterility phenotype itself is also largely rescued by loss of HRDE-1 ( Figure 4D), and, consistent with these data, Phillips et al (2015; in this issue of Developmental Cell) demonstrate that immuno-purified HRDE-1 binds more 22G RNAs from CSR-1 targets during mutator-induced sterility. Interestingly, a wago-1/wago-2/wago-3 triple mutation also rescues the sterility ( Figure 4D).…”

Section: Hrde-1 Is Required To Trigger Mutator-induced Sterilitysupporting

confidence: 74%

Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans

2015

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The Piwi-piRNA pathway represents a germline-specific transposon-defense system. C. elegans Piwi, prg-1, is a non-essential gene and triggers a secondary RNAi response that depends on mutator genes, endo-siRNAs (22G-RNAs), and the 22G-RNA-binding Argonaute protein HRDE-1. Interestingly, silencing of PRG-1 targets can become PRG-1 independent. This state, known as RNAe, is heritable and depends on mutator genes and HRDE-1. We studied how the transgenerational memory of RNAe and the piRNA pathway interact. We find that maternally provided PRG-1 is required for de novo establishment of 22G-RNA populations, especially those targeting transposons. Strikingly, attempts to re-establish 22G-RNAs in absence of both PRG-1 and RNAe memory result in severe germline proliferation defects. This is accompanied by a disturbed balance between gene-activating and -repressing 22G-RNA pathways. We propose a model in which CSR-1 prevents the loading of HRDE-1 and in which both PRG-1 and HRDE-1 help to keep mutator activity focused on the proper targets.

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Section: Hrde-1 Is Required To Trigger Mutator-induced Sterilitysupporting

confidence: 74%

Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans

2015

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“…The 21U‐RNAs interact with PRG‐1, one of the C. elegans Piwi protein homologs, and are also known as the piRNAs of C. elegans (Billi et al , ). In many organisms, the Piwi‐piRNA pathway provides protection against TEs (Luteijn & Ketting, ), and also in C. elegans , 21U‐RNAs contribute to the defense against TE activity (Bagijn et al , ; De Albuquerque et al , ; Phillips et al , ). Interestingly, 21U‐RNAs can initiate a nuclear, 22G‐RNA‐mediated pathway.…”

Section: Introductionmentioning

confidence: 99%

GTSF ‐1 is required for formation of a functional RNA ‐dependent RNA Polymerase complex in Caenorhabditis elegans

Almeida

Dietz²,

Redl

et al. 2018

The EMBO Journal

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Argonaute proteins and their associated small RNAs (sRNAs) are evolutionarily conserved regulators of gene expression. Gametocyte-specific factor 1 (Gtsf1) proteins, characterized by two tandem CHHC zinc fingers and an unstructured C-terminal tail, are conserved in animals and have been shown to interact with Piwi clade Argonautes, thereby assisting their activity. We identified the Gtsf1 homolog, named it and characterized it in the context of the sRNA pathways of We report that GTSF-1 is not required for Piwi-mediated gene silencing. Instead, mutants show a striking depletion of 26G-RNAs, a class of endogenous sRNAs, fully phenocopying mutants. We show, both and , that GTSF-1 interacts with RRF-3 via its CHHC zinc fingers. Furthermore, we demonstrate that GTSF-1 is required for the assembly of a larger RRF-3 and DCR-1-containing complex (ERIC), thereby allowing for 26G-RNA generation. We propose that GTSF-1 homologs may act to drive the assembly of larger complexes that act in sRNA production and/or in imposing sRNA-mediated silencing activities.

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“…In recent years, germline-enriched small non-coding RNAs, such as endogenous siRNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), have been implicated in transposon repression (Batista et al, 2008; Ketting et al, 1999; Tabara et al, 2002). In C. elegans , endo-siRNAs and piRNAs collectively regulate genome defense by targeting deleterious or foreign transcripts, such as transposons, pseudogenes, and transgenes, for repression (Ashe et al, 2012; Batista et al, 2008; Das et al, 2008; de Albuquerque et al, 2015; Han et al, 2009; Kim et al, 2005; Lee et al, 2012; Luteijn et al, 2012; Phillips et al, 2015; Shirayama et al, 2012; Tabara et al, 1999). Furthermore, these pathways are able to regulate gene expression transgenerationally via germline nuclear RNAi (Ashe et al, 2012; Buckley et al, 2012; Grishok et al, 2000; Gu et al, 2012; Luteijn et al, 2012; Shirayama et al, 2012), and, thus, are thought to transmit a memory of genomic “self” and “non-self” elements.…”

Section: Introductionmentioning

confidence: 99%

MORC-1 Integrates Nuclear RNAi and Transgenerational Chromatin Architecture to Promote Germline Immortality

et al. 2017

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Germline-expressed endogenous siRNAs (endo-siRNAs) transmit multigenerational epigenetic information to ensure fertility in subsequent generations. In C. elegans, nuclear RNAi ensures robust inheritance of endo-siRNAs and deposition of repressive H3K9me3 marks at target loci. How target silencing is maintained in subsequent generations is poorly understood. We discovered that morc-1 is essential for transgenerational fertility and acts as an effector of endo-siRNAs. Unexpectedly, morc-1 is dispensable for siRNA inheritance but required for target silencing and maintenance of siRNA-dependent chromatin organization. A forward genetic screen identified mutations in met-1, which encodes a H3K36 methyltransferase, as potent suppressors of morc-1(−) and nuclear RNAi mutant phenotypes. Further analysis of nuclear RNAi and morc-1(−) mutants revealed a progressive, met-1-dependent enrichment of H3K36me3, suggesting that robust fertility requires repression of MET-1 activity at nuclear RNAi targets. Without MORC-1 and nuclear RNAi, MET-1-mediated encroachment of euchromatin leads to detrimental decondensation of germline chromatin and germline mortality.

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piRNAs and piRNA-Dependent siRNAs Protect Conserved and Essential C. elegans Genes from Misrouting into the RNAi Pathway

Cited by 84 publications

References 29 publications

Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans

Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans

GTSF ‐1 is required for formation of a functional RNA ‐dependent RNA Polymerase complex in Caenorhabditis elegans

MORC-1 Integrates Nuclear RNAi and Transgenerational Chromatin Architecture to Promote Germline Immortality

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