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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cell Nucleus / metabolism*
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Cytoplasm / metabolism*
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Genes, Helminth
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Mutation
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Nuclear Localization Signals
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Protein Structure, Tertiary
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RNA Interference*
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RNA Precursors / genetics
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RNA Precursors / metabolism
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RNA, Double-Stranded / chemistry
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / metabolism
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RNA, Helminth / chemistry
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RNA, Helminth / genetics
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RNA, Helminth / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / chemistry
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism*
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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RNA-Dependent RNA Polymerase / metabolism
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Up-Regulation
Substances
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Caenorhabditis elegans Proteins
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NRDE-3 protein, C elegans
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Nuclear Localization Signals
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RNA Precursors
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RNA, Double-Stranded
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RNA, Helminth
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RNA, Messenger
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RNA, Small Interfering
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RNA-Binding Proteins
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RNA-Dependent RNA Polymerase