title: Endogenous nuclear RNAi mediates behavioral adaptation to odor.
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:
authors.affiliation: Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA.
authors.forename: Bi-Tzen
authors.initials: BT
authors.lastname: Juang
authors.affiliation: 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.
authors.forename: Chen
authors.initials: C
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Linda
authors.initials: L
authors.lastname: Starnes
authors.affiliation: École Normale Supérieure de Lyon, CNRS, Molecular Biology of the Cell Laboratory/ UMR5239, Université Claude Bernard Lyon, 69007 Lyon, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Palladino
authors.affiliation: Departments of Cell & Tissue Biology and Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Goga
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: 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.
authors.forename: Noelle D
authors.initials: ND
authors.lastname: L'Etoile
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002074:Butanones / Q000737:chemistry; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D006162:Guanylate Cyclase / Q000235:genetics*; D009812:Odorants; D010766:Phosphorylation; D034622:RNA Interference; D018510:RNA, Helminth / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*
chemical_list: D002074:Butanones; D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; C514742:HPL-2 protein, C elegans; C530516:NRDE-3 protein, C elegans; D018510:RNA, Helminth; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017869:Cyclic GMP-Dependent Protein Kinases; C470349:EGL-4 protein, C elegans; D006162:Guanylate Cyclase; C584108:ODR-1 protein, C elegans