Journal
CELL REPORTS
Volume 6, Issue 1, Pages 211-221Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2013.12.013
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Funding
- National Institutes of Health [1F32HD060377, GM 73042, GM85080]
- Welch Foundation [I-1244]
- Cancer Prevention and Research Institute of Texas [RP120311]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [F32HD060377] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM073042, R01GM085080] Funding Source: NIH RePORTER
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RNAi is widely appreciated as a powerful regulator of mRNA translation in the cytoplasm of mammalian cells. However, the presence and activity of RNAi factors in the mammalian nucleus has been the subject of considerable debate. Here, we show that Argonaute-2 (Ago2) and RNAi factors Dicer, TRBP, and TRNC6A/GW182 are in the human nucleus and associate together in multiprotein complexes. Small RNAs can silence nuclear RNA and guide site-specific cleavage of the targeted RNA, demonstrating that RNAi can function in the human nucleus. Nuclear Dicer is active and miRNAs are bound to nuclear Ago2, consistent with the existence of nuclear miRNA pathways. Notably, we do not detect loading of duplex small RNAs in nuclear extracts and known loading factors are absent. These results extend RNAi into the mammalian nucleus and suggest that regulation of RNAi via small RNA loading of Ago2 differs between the cytoplasm and the nucleus.
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