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
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- 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, 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*
- RNA-Dependent RNA Polymerase / metabolism
- Up-Regulation
Substances
- Caenorhabditis elegans Proteins
- NRDE-3 protein, C elegans
- Nuclear Localization Signals
- RNA Precursors
- RNA, Double-Stranded
- RNA, Helminth
- RNA, Messenger
- RNA, Small Interfering
- RNA-Binding Proteins
- RNA-Dependent RNA Polymerase