The conserved helicase ZNFX-1 memorializes silenced RNAs in perinuclear condensates View Full Text


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Article Info

DATE

2022-06-23

AUTHORS

John Paul Tsu Ouyang, Wenyan Lucy Zhang, Geraldine Seydoux

ABSTRACT

RNA-mediated interference (RNAi) is a conserved mechanism that uses small RNAs (sRNAs) to silence gene expression. In the Caenorhabditis elegans germline, transcripts targeted by sRNAs are used as templates for sRNA amplification to propagate silencing into the next generation. Here we show that RNAi leads to heritable changes in the distribution of nascent and mature transcripts that correlate with two parallel sRNA amplification loops. The first loop, dependent on the nuclear Argonaute HRDE-1, targets nascent transcripts and reduces but does not eliminate productive transcription at the locus. The second loop, dependent on the conserved helicase ZNFX-1, targets mature transcripts and concentrates them in perinuclear condensates. ZNFX-1 interacts with sRNA-targeted transcripts that have acquired poly(UG) tails and is required to sustain pUGylation and robust sRNA amplification in the inheriting generation. By maintaining a pool of transcripts for amplification, ZNFX-1 prevents premature extinction of the RNAi response and extends silencing into the next generation. More... »

PAGES

1129-1140

References to SciGraph publications

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  • 2005-06-05. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies in NATURE CELL BIOLOGY
  • 2017-02-15. Decoupling the downstream effects of germline nuclear RNAi reveals that H3K9me3 is dispensable for heritable RNAi and the maintenance of endogenous siRNA-mediated transcriptional silencing in Caenorhabditis elegans in EPIGENETICS & CHROMATIN
  • 2010-06-13. Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription in NATURE
  • 2012-06-28. Meiotic Development in Caenorhabditis elegans in GERM CELL DEVELOPMENT IN C. ELEGANS
  • 2020-05-20. poly(UG)-tailed RNAs in genome protection and epigenetic inheritance in NATURE
  • 2020-02-03. Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants in NATURE CELL BIOLOGY
  • 2012-07-18. A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality in NATURE
  • 2015-03-09. HISAT: a fast spliced aligner with low memory requirements in NATURE METHODS
  • 2012-12-23. Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41556-022-00940-w

    DOI

    http://dx.doi.org/10.1038/s41556-022-00940-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1148902882

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35739318


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