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RNAi factors are present and active in human cell nuclei.

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-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.

SUBMITTER: Gagnon KT

PROVIDER: S-EPMC3916906 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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RNAi factors are present and active in human cell nuclei.

Gagnon Keith T KT Li Liande L Chu Yongjun Y Janowski Bethany A BA Corey David R DR

Cell reports 20140102 1

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 RNA ...[more]

PMID: 24388755

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