Endogenous Nuclear RNAi Mediates Behavioral Adaptation to Odor

Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA.
Cell (Impact Factor: 32.24). 08/2013; 154(5):1010-22. DOI: 10.1016/j.cell.2013.08.006
Source: PubMed


Most eukaryotic cells express small regulatory RNAs. The purpose of one class, the somatic endogenous siRNAs (endo-siRNAs), remains unclear. Here, we show that 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 whose downregulation 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. PAPERFLICK:

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    • "Recently, we reported that the endogenous nuclear interference RNA (RNAi) pathway (48) is required in AWC for olfactory adaptation (33). The endogenously-produced small RNAs that we found to be required for odor adaptation are amplified from mRNA by an RNA-dependent RNA polymerase; therefore, these 22-nt RNAs are antisense to the original template. "
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