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Science 319 (5871): 1789-1790

Copyright © 2008 by the American Association for the Advancement of Science

Multilevel Regulation of Gene Expression by MicroRNAs

Eugene V. Makeyev, and Tom Maniatis

Abstract: MicroRNAs (miRNAs) are ~22-nucleotide-long noncoding RNAs that normally function by suppressing translation and destabilizing messenger RNAs bearing complementary target sequences. Some miRNAs are expressed in a cell- or tissue-specific manner and may contribute to the establishment and/or maintenance of cellular identity. Recent studies indicate that tissue-specific miRNAs may function at multiple hierarchical levels of gene regulatory networks, from targeting hundreds of effector genes incompatible with the differentiated state to controlling the levels of global regulators of transcription and alternative pre-mRNA splicing. This multilevel regulation may allow individual miRNAs to profoundly affect the gene expression program of differentiated cells.

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. E-mail: makeyev{at} (E.V.M.); maniatis{at} (T.M.)

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c-MYC-regulated miR-23a/24-2/27a Cluster Promotes Mammary Carcinoma Cell Invasion and Hepatic Metastasis by Targeting Sprouty2.
X. Li, X. Liu, W. Xu, P. Zhou, P. Gao, S. Jiang, P. E. Lobie, and T. Zhu (2013)
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miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-{alpha} activation.
Y. Fang, X. Yu, Y. Liu, A. J. Kriegel, Y. Heng, X. Xu, M. Liang, and X. Ding (2013)
Am J Physiol Renal Physiol 304, F1274-F1282
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miR-206 regulates the growth of the teleost tilapia (Oreochromis niloticus) through the modulation of IGF-1 gene expression.
B. Yan, C.-D. Zhu, J.-T. Guo, L.-H. Zhao, and J.-L. Zhao (2013)
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miR-203b: a novel regulator of MyoD expression in tilapia skeletal muscle.
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J. Exp. Biol. 216, 447-451
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Argonaute identity defines the length of mature mammalian microRNAs.
P. K. Juvvuna, P. Khandelia, L. M. Lee, and E. V. Makeyev (2012)
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The Cambrian Conundrum: Early Divergence and Later Ecological Success in the Early History of Animals.
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Science 334, 1091-1097
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MicroRNA Expression Profiles of Human Blood Monocyte-derived Dendritic Cells and Macrophages Reveal miR-511 as Putative Positive Regulator of Toll-like Receptor 4.
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J. Biol. Chem. 286, 26487-26495
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Paleobiology 37, 214-236
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miRNA malfunction causes spinal motor neuron disease.
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MicroRNA-204/211 alters epithelial physiology.
F. E. Wang, C. Zhang, A. Maminishkis, L. Dong, C. Zhi, R. Li, J. Zhao, V. Majerciak, A. B. Gaur, S. Chen, et al. (2010)
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Understanding neuronal connectivity through the post-transcriptional toolkit.
C. M. Loya, D. Van Vactor, and T. A. Fulga (2010)
Genes & Dev. 24, 625-635
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Renal Medullary MicroRNAs in Dahl Salt-Sensitive Rats: miR-29b Regulates Several Collagens and Related Genes.
Y. Liu, N. E. Taylor, L. Lu, K. Usa, A. W. Cowley Jr, N. R. Ferreri, N. C. Yeo, and M. Liang (2010)
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Autoregulation of Fox protein expression to produce dominant negative splicing factors.
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RNA 16, 405-416
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Nucleic Acids Res. 37, 5969-5980
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Am J Physiol Renal Physiol 297, F553-F558
   Abstract »    Full Text »    PDF »
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S. D. N. Reddy, S. B. Pakala, K. Ohshiro, S. K. Rayala, and R. Kumar (2009)
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MicroRNA: a new entrance to the broad paradigm of systems molecular medicine.
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Physiol Genomics 38, 113-115
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C.-I Wu, Y. Shen, and T. Tang (2009)
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Small RNA Pathways Are Present and Functional in the Angiosperm Male Gametophyte.
R. Grant-Downton, S. Hafidh, D. Twell, and H. G. Dickinson (2009)
Mol Plant 2, 500-512
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Auto- and Cross-Regulation of the hnRNP L Proteins by Alternative Splicing.
O. Rossbach, L.-H. Hung, S. Schreiner, I. Grishina, M. Heiner, J. Hui, and A. Bindereif (2009)
Mol. Cell. Biol. 29, 1442-1451
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Cutting Edge: Down-Regulation of MHC Class I-Related Chain A on Tumor Cells by IFN-{gamma}-Induced MicroRNA.
D. Yadav, J. Ngolab, R. S.-H. Lim, S. Krishnamurthy, and J. D. Bui (2009)
J. Immunol. 182, 39-43
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Mapping Key Features of Transcriptional Regulatory Circuitry in Embryonic Stem Cells.
M.F. Cole and R.A. Young (2008)
Cold Spring Harb Symp Quant Biol
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MicroRNA-7, a Homeobox D10 Target, Inhibits p21-Activated Kinase 1 and Regulates Its Functions.
S. D. N. Reddy, K. Ohshiro, S. K. Rayala, and R. Kumar (2008)
Cancer Res. 68, 8195-8200
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The Eukaryotic Genome as an RNA Machine.
P. P. Amaral, M. E. Dinger, T. R. Mercer, and J. S. Mattick (2008)
Science 319, 1787-1789
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