RNAi factors are present and active in human cell nuclei

KeithT Gagnon, Liande Li, Yongjun Chu, BethanyA Janowski, DavidR Corey

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

Abstract

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-specificcleavage 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.

Original languageEnglish (US)
Pages (from-to)211-221
Number of pages11
JournalCell Reports
Volume6
Issue number1
DOIs
StatePublished - Jan 3 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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