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

Endogenous nuclear RNAi mediates behavioral adaptation to odor.

Author information

1
Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA.
2
Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA; Amunix, Inc., 500 Ellis Street, Mountain View, CA 94043, USA.
3
Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA; Chromatin Structure and Function Group, NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, Room 4.3.07, 2200 Copenhagen N, Denmark.
4
École Normale Supérieure de Lyon, CNRS, Molecular Biology of the Cell Laboratory/ UMR5239, Université Claude Bernard Lyon, 69007 Lyon, France.
5
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
6
Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA. Electronic address: noelle.letoile@ucsf.edu.

Abstract

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.

PMID:
23993094
PMCID:
PMC4274153
DOI:
10.1016/j.cell.2013.08.006
[Indexed for MEDLINE]
Free PMC Article

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