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Science 25 July 2008:
Vol. 321. no. 5888, pp. 537 - 541
DOI: 10.1126/science.1157647
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Research Articles

An Argonaute Transports siRNAs from the Cytoplasm to the Nucleus

Shouhong Guang,1* Aaron F. Bochner,1,2* Derek M. Pavelec,1,3 Kirk B. Burkhart,1,4 Sandra Harding,1 Jennifer Lachowiec,1 Scott Kennedy1{dagger}

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.

1 Department of Pharmacology, University of Wisconsin–Madison, Madison, WI 53706, USA.
2 Program in Cellular and Molecular Biology, University of Wisconsin–Madison, Madison, WI 53706, USA.
3 Program in Molecular and Cellular Pharmacology, University of Wisconsin–Madison, Madison, WI 53706, USA.
4 Department of Genetics, University of Wisconsin–Madison, Madison, WI 53706, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sgkennedy{at}wisc.edu

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