Endogenous Nuclear RNAi Mediates Behavioral Adaptation to Odor

Abstract

Summary Most eukaryotic cells express small regulatory RNAs. The purpose of one class, the somatic endogenous siRNAs (endo-siRNAs) remains unclear. Here we show the endo-siRNA pathway promotes odor adaptation in C. elegans AWC olfactory neurons. In adaptation, the nuclear Argonaute NRDE-3, which acts in AWC, is loaded with siRNAs targeting odr-1, a gene who's down regulation is required for adaptation. Concomitant with increased odr-1 siRNA in AWC, we observe increased binding of the HP1 homolog HPL-2 at the odr-1 locus in AWC and reduced odr-1 mRNA in adapted animals. Phosphorylation of HPL-2, an in vitro substrate of the EGL-4 kinase that promotes adaption, is necessary and sufficient for behavioral adaptation. Thus, environmental stimulation amplifies an endo-siRNA negative feedback loop to dynamically repress cognate gene expression and shape behavior. This class of siRNA may act broadly as a rheostat allowing prolonged stimulation to dampen gene expression and promote cellular memory formation.

The Importance of cGMP Signaling in Sensory Cilia for Body Size Regulation in Caenorhabditis elegans

“…For example, in the process of odorant adaptation, activation of EGL-4 by ODR-1 is thought to induce the downregulation of ODR-1 (Juang et al 2013). Without independent GC partners, such a feedback regulation would affect other processes in which EGL-4 is involved.…”

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

“…Here, we describe a novel role for RDE-4 in embryonic neuronal migration, which is consistent with previous observations that the generation of some somatic 22G-RNAs is dependent on RDE-4 ( Lee et al 2006;Gu et al 2009). Interestingly, RDE-4 has also been recently shown to participate in the production of endogenous 22G-RNAs required to mediate odor adaptation in adult animals (Juang et al 2013).…”

Systematic comparison of bacterial feeding strains for increased yield of Caenorhabditis elegans males by RNA interference‐induced non‐disjunction

“…Thus, in addition to the defects in mut-7 and rde-2 mutants that contribute to germline non-disjunction, the animals also harbor defects that persist into later developmental stages, affecting fertility in adult males. Indeed, endogenous siRNAi defects in mut-7 have been correlated with odor adaptation in AWC neurons of adults [24]. We investigated the nature of the fertility defects in mut-7 and rde-2 mutant males, and we found that the males were capable of producing progeny when the hermaphrodite parent was unc (paralyzed), suggesting that mutant males are defective in movements that are required for effective mating (Table 3).…”