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

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The conserved helicase ZNFX-1 memorializes silenced RNAs in perinuclear condensates
The conserved helicase ZNFX-1 memorializes silenced RNAs in perinuclear condensates
Journal Article

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

2022
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Overview
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. Ouyang et al. show that the RNA helicase ZNFX-1 preserves heritable RNAi by maintaining a pool of small RNA-targeted transcripts in perinuclear condensates of the Caenorhabditis elegans germline, which serve as templates for small-RNA amplification in the next generation.