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Dual roles for piRNAs in promoting and preventing transgenerational gene silencing in C. elegans

ABSTRACT: Dual roles for piRNAs in promoting and preventing transgenerational gene silencing in C. elegans

PROVIDER: PRJNA745159 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15084812.fastq.gz	Fastqsanger.gz
	SRR15084813.fastq.gz	Fastqsanger.gz
	SRR15084814.fastq.gz	Fastqsanger.gz
	SRR15084815.fastq.gz	Fastqsanger.gz
	SRR15084816.fastq.gz	Fastqsanger.gz

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Dual roles for piRNAs in promoting and preventing transgenerational gene silencing in C. elegans

Project description:To explore the roles of piRNAs in regulating 22G-RNA production and transgenerational gene silencing, we used RNA-seq to assess changes in small RNA and mRNA levels in piwi/prg-1 and mutator mutants at an early generation and again at a late generation. We identified that in the absence of piRNAs, many genes gain 22G-RNAs which in turn guide transgenerational gene silencing.

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Dual roles for piRNAs in promoting and preventing gene silencing in C. elegans.

Project description:Piwi-interacting RNAs (piRNAs) regulate many biological processes through mechanisms that are not fully understood. In Caenorhabditis elegans, piRNAs intersect the endogenous RNA interference (RNAi) pathway, involving a distinct class of small RNAs called 22G-RNAs, to regulate gene expression in the germline. In the absence of piRNAs, 22G-RNA production from many genes is reduced, pointing to a role for piRNAs in facilitating endogenous RNAi. Here, however, we show that many genes gain, rather than lose, 22G-RNAs in the absence of piRNAs, which is in some instances coincident with RNA silencing. Aberrant 22G-RNA production is somewhat stochastic but once established can occur within a population for at least 50 generations. Thus, piRNAs both promote and suppress 22G-RNA production and gene silencing. rRNAs and histones are hypersusceptible to aberrant silencing, but we do not find evidence that their misexpression is the primary cause of the transgenerational sterility observed in piRNA-defective mutants.

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Project description:PIWI-interacting RNAs (piRNAs) promote fertility in many animals. Yet, whether this is due to their conserved role in repressing repetitive elements (REs) remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets, but rather mediated by the epigenetic silencing of all the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway restores histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that the sRNA-mediated silencing of histone genes impairs fertility of piRNA mutants and may serve to maintain piRNAs across evolution.

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Project description:PIWI-interacting RNAs (piRNAs) promote fertility in many animals. Yet, whether this is due to their conserved role in repressing repetitive elements (REs) remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets, but rather mediated by the epigenetic silencing of all the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway restores histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that the sRNA-mediated silencing of histone genes impairs fertility of piRNA mutants and may serve to maintain piRNAs across evolution.

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