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Guang, S, Bochner, AF, Pavelec, DM, Burkhart, KB, Harding, S, Lachowiec, J and Kennedy, S (2008) An Argonaute transports siRNAs from the cytoplasm to the nucleus. Science 321:537-41


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.


PubMed PMC2771369 Online version:10.1126/science.1157647


Active Transport, Cell Nucleus; Animals; Caenorhabditis elegans/embryology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/growth & development; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Nucleus/metabolism; Cytoplasm/metabolism; Genes, Helminth; Mutation; Nuclear Localization Signals; Protein Structure, Tertiary; RNA Interference; RNA Precursors/genetics; RNA Precursors/metabolism; RNA Replicase/metabolism; RNA, Double-Stranded/chemistry; RNA, Double-Stranded/genetics; RNA, Double-Stranded/metabolism; RNA, Helminth/chemistry; RNA, Helminth/genetics; RNA, Helminth/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA, Small Interfering/chemistry; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Up-Regulation