title: An Argonaute transports siRNAs from the cytoplasm to the nucleus.
abstract: Ribonucleoprotein complexes consisting of Argonaute-like proteins and small regulatory RNAs function in a wide range of biological processes. Many of these small regulatory RNAs are predicted to act, at least in part, within the nucleus. We conducted a genetic screen to identify factors essential for RNA interference (RNAi) in nuclei of Caenorhabditis elegans and identified the Argonaute protein NRDE-3. In the absence of small interfering RNAs (siRNAs), NRDE-3 resides in the cytoplasm. NRDE-3 binds siRNAs generated by RNA-dependent RNA polymerases acting on messenger RNA templates in the cytoplasm and redistributes to the nucleus. Nuclear redistribution of NRDE-3 requires a functional nuclear localization signal, is required for nuclear RNAi, and results in NRDE-3 association with nuclear-localized nascent transcripts. Thus, specific Argonaute proteins can transport specific classes of small regulatory RNAs to distinct cellular compartments to regulate gene expression.
authors.affiliation: Department of Pharmacology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Guang
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Bochner
authors.forename: Derek M
authors.initials: DM
authors.lastname: Pavelec
authors.forename: Kirk B
authors.initials: KB
authors.lastname: Burkhart
authors.forename: Sandra
authors.initials: S
authors.lastname: Harding
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lachowiec
authors.forename: Scott
authors.initials: S
authors.lastname: Kennedy
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D017238:Genes, Helminth; D009154:Mutation; D019913:Nuclear Localization Signals; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018510:RNA, Helminth / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; C530516:NRDE-3 protein, C elegans; D019913:Nuclear Localization Signals; D012322:RNA Precursors; D012330:RNA, Double-Stranded; D018510:RNA, Helminth; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012324:RNA-Dependent RNA Polymerase