Neuronal Small RNAs Control Behavior Transgenerationally

Summary

It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study, we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous small interfering RNAs (siRNAs) and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs, we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small-RNA-based mechanism for communication of neuronal processes transgenerationally.

Graphical Abstract

Highlights

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  C. elegans neuronal small RNAs are characterized by RNA sequencing

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  RDE-4-dependent neuronal endogenous small RNAs communicate with the germline

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  Germline HRDE-1 mediates transgenerational regulation by neuronal small RNAs

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  Neuronal small RNAs regulate germline genes to control behavior transgenerationally

Abstract

The idea that brain activity can impact the fate of the progeny goes against a central tenet of biology. Posner et al. describe an RNA-based mechanism for how neuronal responses to environmental cues can be translated into heritable information that affects the behavior of progeny.