Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans

• Starvation in C. elegans induces transgenerational inheritance of small RNAs
• Inherited small RNAs target genes that are involved in nutrition
• RNA-binding proteins RDE-4 and HRDE-1 are required for transgenerational inheritance
• Progeny that derive from L1-starved ancestors have extended longevity

SummaryEvidence from animal studies and human famines suggests that starvation may affect the health of the progeny of famished individuals. However, it is not clear whether starvation affects only immediate offspring or has lasting effects; it is also unclear how such epigenetic information is inherited. Small RNA-induced gene silencing can persist over several generations via transgenerationally inherited small RNA molecules in C. elegans, but all known transgenerational silencing responses are directed against foreign DNA introduced into the organism. We found that starvation-induced developmental arrest, a natural and drastic environmental change, leads to the generation of small RNAs that are inherited through at least three consecutive generations. These small, endogenous, transgenerationally transmitted RNAs target genes with roles in nutrition. We defined genes that are essential for this multigenerational effect. Moreover, we show that the F3 offspring of starved animals show an increased lifespan, corroborating the notion of a transgenerational memory of past conditions.

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