RESUMEN
Nuage are RNA-rich condensates that assemble around the nuclei of developing germ cells. Many proteins required for the biogenesis and function of silencing small RNAs (sRNAs) enrich in nuage, and it is often assumed that nuage is the cellular site where sRNAs are synthesized and encounter target transcripts for silencing. Using C. elegans as a model, we examine the complex multicondensate architecture of nuage and review evidence for compartmentalization of silencing pathways. We consider the possibility that nuage condensates balance the activity of competing sRNA pathways and serve to limit, rather than enhance, sRNA amplification to protect transcripts from dangerous runaway silencing.
Asunto(s)
Condensados Biomoleculares/química , Proteínas de Caenorhabditis elegans/química , Caenorhabditis elegans/química , Interferencia de ARN , ARN de Helminto/química , ARN Interferente Pequeño/química , Animales , Proteínas Argonautas/química , Proteínas Argonautas/metabolismo , Condensados Biomoleculares/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Compartimento Celular , Núcleo Celular/metabolismo , Núcleo Celular/ultraestructura , Embrión no Mamífero , Gránulos de Ribonucleoproteína de Células Germinales/metabolismo , Gránulos de Ribonucleoproteína de Células Germinales/ultraestructura , Células Germinativas/metabolismo , Células Germinativas/ultraestructura , ARN de Helminto/metabolismo , ARN Interferente Pequeño/metabolismoRESUMEN
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.