Endogenous nuclear RNAi mediates behavioral adaptation to odor

Cell. 2013 Aug 29;154(5):1010-1022. doi: 10.1016/j.cell.2013.08.006.


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:

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Butanones / chemistry
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Down-Regulation*
  • Guanylate Cyclase / genetics*
  • Odorants
  • Phosphorylation
  • RNA Interference*
  • RNA, Helminth / metabolism
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / metabolism
  • Sensory Receptor Cells / metabolism*


  • Butanones
  • Caenorhabditis elegans Proteins
  • Chromosomal Proteins, Non-Histone
  • HPL-2 protein, C elegans
  • NRDE-3 protein, C elegans
  • RNA, Helminth
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Cyclic GMP-Dependent Protein Kinases
  • EGL-4 protein, C elegans
  • Guanylate Cyclase
  • ODR-1 protein, C elegans