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Vol. 17, No. 4, pp. 438-442, February 15, 2003

RESEARCH COMMUNICATION
siRNAs can function as miRNAs

John G. Doench,1,3 Christian P. Petersen,1,3 and Phillip A. Sharp1,2,4

1 Center for Cancer Research, Department of Biology, and 2 McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

With the discovery of RNA interference (RNAi) and related phenomena, new regulatory roles attributed to RNA continue to emerge. Here we show, in mammalian tissue culture, that a short interfering RNA (siRNA) can repress expression of a target mRNA with partially complementary binding sites in its 3' UTR, much like the demonstrated function of endogenously encoded microRNAs (miRNAs). The mechanism for this repression is cooperative, distinct from the catalytic mechanism of mRNA cleavage by siRNAs. The use of siRNAs to study translational repression holds promise for dissecting the sequence and structural determinants and general mechanism of gene repression by miRNAs.

[Keywords: siRNA; miRNA; RNAi; translational repression; 3' UTR]


3 These authors contributed equally.

4 Corresponding author.


© 2003 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/03 $5.00

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[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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Home page
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[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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J. Virol., November 1, 2006; 80(21): 10890 - 10893.
[Abstract] [Full Text] [PDF]


Home page
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S. Chiosea, E. Jelezcova, U. Chandran, M. Acquafondata, T. McHale, R. W. Sobol, and R. Dhir
Up-Regulation of Dicer, a Component of the MicroRNA Machinery, in Prostate Adenocarcinoma
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[Abstract] [Full Text] [PDF]


Home page
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Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells
Nucleic Acids Res., October 18, 2006; 34(17): 4801 - 4815.
[Abstract] [Full Text] [PDF]


Home page
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H. K. Kim, Y. S. Lee, U. Sivaprasad, A. Malhotra, and A. Dutta
Muscle-specific microRNA miR-206 promotes muscle differentiation
J. Cell Biol., August 28, 2006; 174(5): 677 - 687.
[Abstract] [Full Text] [PDF]


Home page
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M. M. Martin, E. J. Lee, J. A. Buckenberger, T. D. Schmittgen, and T. S. Elton
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J. Biol. Chem., July 7, 2006; 281(27): 18277 - 18284.
[Abstract] [Full Text] [PDF]


Home page
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[Abstract] [Full Text] [PDF]


Home page
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Comprehensive thermodynamic analysis of 3' double-nucleotide overhangs neighboring Watson-Crick terminal base pairs
Nucleic Acids Res., July 4, 2006; 34(11): 3338 - 3344.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
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A novel class of small RNAs in mouse spermatogenic cells
Genes & Dev., July 1, 2006; 20(13): 1709 - 1714.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
E. Gottwein, X. Cai, and B. R. Cullen
A Novel Assay for Viral MicroRNA Function Identifies a Single Nucleotide Polymorphism That Affects Drosha Processing.
J. Virol., June 1, 2006; 80(11): 5321 - 5326.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
T. Reuter, B. Weissbrich, S. Schneider-Schaulies, and J. Schneider-Schaulies
RNA Interference with Measles Virus N, P, and L mRNAs Efficiently Prevents and with Matrix Protein mRNA Enhances Viral Transcription.
J. Virol., June 1, 2006; 80(12): 5951 - 5957.
[Abstract] [Full Text] [PDF]


Home page
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C. M. Rondinone
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Endocrinology, June 1, 2006; 147(6): 2650 - 2656.
[Abstract] [Full Text] [PDF]


Home page
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U. Muckstein, H. Tafer, J. Hackermuller, S. H. Bernhart, P. F. Stadler, and I. L. Hofacker
Thermodynamics of RNA-RNA binding
Bioinformatics, May 15, 2006; 22(10): 1177 - 1182.
[Abstract] [Full Text] [PDF]


Home page
Nucleic Acids ResHome page
K.-H. Chung, C. C. Hart, S. Al-Bassam, A. Avery, J. Taylor, P. D. Patel, A. B. Vojtek, and D. L. Turner
Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155
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[Abstract] [Full Text] [PDF]


Home page
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PNAS, April 11, 2006; 103(15): 5953 - 5958.
[Abstract] [Full Text] [PDF]


Home page
J Biomol ScreenHome page
L. H. Lamarcq, B. J. Scherer, M. L. Phelan, N. N. Kalnine, Y. H. Nguyen, T. Kabakova, X. Chen, M. Tan, C. Chang, C. Berlon, et al.
Large-Scale, High-Throughput Validation of Short Hairpin RNA Sequences for RNA Interference
J Biomol Screen, April 1, 2006; 11(3): 236 - 246.
[Abstract] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
L. Wu, J. Fan, and J. G. Belasco
From the Cover: MicroRNAs direct rapid deadenylation of mRNA
PNAS, March 14, 2006; 103(11): 4034 - 4039.
[Abstract] [Full Text] [PDF]


Home page
Nucleic Acids ResHome page
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In situ fluorescence analysis demonstrates active siRNA exclusion from the nucleus by Exportin 5
Nucleic Acids Res., March 6, 2006; 34(5): 1369 - 1380.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
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Transcriptional Origin of Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs
J. Virol., March 1, 2006; 80(5): 2234 - 2242.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
C. Simon-Mateo and J. A. Garcia
MicroRNA-Guided Processing Impairs Plum Pox Virus Replication, but the Virus Readily Evolves To Escape This Silencing Mechanism
J. Virol., March 1, 2006; 80(5): 2429 - 2436.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
M. A. Valencia-Sanchez, J. Liu, G. J. Hannon, and R. Parker
Control of translation and mRNA degradation by miRNAs and siRNAs.
Genes & Dev., March 1, 2006; 20(5): 515 - 524.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
J. Wittmann, E. M. Hol, and H.-M. Jack
hUPF2 Silencing Identifies Physiologic Substrates of Mammalian Nonsense-Mediated mRNA Decay
Mol. Cell. Biol., February 15, 2006; 26(4): 1272 - 1287.
[Abstract] [Full Text] [PDF]


Home page
Nucleic Acids ResHome page
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High potency silencing by single-stranded boranophosphate siRNA.
Nucleic Acids Res., January 1, 2006; 34(9): 2773 - 2781.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
P. J. Atkinson, K. W. Young, S. J. Ennion, J. N. C. Kew, S. R. Nahorski, and R. A. J. Challiss
Altered Expression of Gq/11{alpha} Protein Shapes mGlu1 and mGlu5 Receptor-Mediated Single Cell Inositol 1,4,5-Trisphosphate and Ca2+ Signaling
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[Abstract] [Full Text] [PDF]