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Involvement of AGO1 and AGO2 in mammalian transcriptional silencing

Janowski, Bethany A, Huffman, Kenneth E, Schwartz, Jacob C, Ram, Rosalyn, Nordsell, Robert, Shames, David S, Minna, John D, Corey, David R·2006·Nature Structural & Molecular Biology
DOI 10.1038/nsmb1140
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Abstract

Duplex RNAs complementary to messenger RNA inhibit translation in mammalian cells by RNA interference (RNAi). Studies have reported that RNAs complementary to promoter DNA also inhibit gene expression. Here we show that the human homologs of Argonaute-1 (AGO1) and Argonaute-2 (AGO2) link the silencing pathways that target mRNA with pathways mediating recognition of DNA. We find that synthetic antigene RNAs (agRNAs) complementary to transcription start sites or more upstream regions of gene promoters inhibit gene transcription. This silencing occurs in the nucleus, requires high promoter activity and does not necessarily require histone modification. AGO1 and AGO2 associate with promoter DNA in cells treated with agRNAs, and inhibiting expression of AGO1 or AGO2 reverses transcriptional and post-transcriptional silencing. Our data indicate key linkages and important mechanistic distinctions between transcriptional and post-transcriptional silencing pathways in mammalian cells.

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Research works printed but not linked: 35

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Metadata

Authors
Janowski, B. A., Huffman, K. E., Schwartz, J. C., Ram, R., Nordsell, R., Shames, D. S., Minna, J. D., & Corey, D. R.
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2006-08-27
Volume
13
Issue
9
Pages
787-792
ISSN
  • 1545-9993
  • 1545-9985
DOI
10.1038/nsmb1140
Cited by
288
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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