Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 2 January 2007
Vol. 2007, Issue 367, p. re1
[DOI: 10.1126/stke.3672007re1]


How Do MicroRNAs Regulate Gene Expression?

Richard J. Jackson* and Nancy Standart*

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.

Gloss: The human genome encodes several hundred short (~21 residue) microRNAs (miRNAs), which are predicted to collectively regulate several thousand distinct genes, amounting to about one-third of all human genes. MicroRNAs generally interact with their target mRNAs through imperfect or incomplete complementary base-pairing to sites in the 3'-untranslated region of the messenger RNA (mRNA), which are usually present in multiple copies. These interactions result in a decrease in synthesis of the protein encoded by the mRNA, but until very recently, little was known about the mechanism(s) of this repression. An miRNA can decrease the intracellular concentration of its target mRNAs by accelerating the normal process of mRNA degradation and can inhibit the translation or decoding of the target mRNA, with the relative importance of these two mechanisms differing between different miRNA-mRNA pairs. The mechanism of inhibition of translation remains controversial, with some data pointing to inhibition of the translation initiation step, and other results indicative of inhibition at some later stage during the actual decoding of the mRNA sequence. This article reviews these recent data, discusses the controversies that remain unresolved, and makes suggestions for future research.

*E-mail: rjj{at} (R.J.J.); nms{at} (N.S.)

Citation: R. J. Jackson, N. Standart, How Do MicroRNAs Regulate Gene Expression? Sci. STKE 2007, re1 (2007).

The transcriptomic and proteomic effects of ectopic overexpression of miR-30d in human endometrial epithelial cells.
J. M. Moreno-Moya, F. Vilella, S. Martinez, A. Pellicer, and C. Simon (2014)
Mol. Hum. Reprod.
   Abstract »    Full Text »    PDF »
VEGF controls lung Th2 inflammation via the miR-1-Mpl (myeloproliferative leukemia virus oncogene)-P-selectin axis.
S. Takyar, H. Vasavada, J.-g. Zhang, F. Ahangari, N. Niu, Q. Liu, C. G. Lee, L. Cohn, and J. A. Elias (2013)
J. Exp. Med. 210, 1993-2010
   Abstract »    Full Text »    PDF »
Epigenetics and Psychostimulant Addiction.
H. D. Schmidt, J. F. McGinty, A. E. West, and G. Sadri-Vakili (2013)
Cold Spring Harb Perspect Med 3, a012047
   Abstract »    Full Text »    PDF »
Regulation of Expression of Deoxyhypusine Hydroxylase (DOHH), the Enzyme That Catalyzes the Activation of eIF5A, by miR-331-3p and miR-642-5p in Prostate Cancer Cells.
M. R. Epis, K. M. Giles, F. C. Kalinowski, A. Barker, R. J. Cohen, and P. J. Leedman (2012)
J. Biol. Chem. 287, 35251-35259
   Abstract »    Full Text »    PDF »
Right- and left-loop short shRNAs have distinct and unusual mechanisms of gene silencing.
A. Dallas, H. Ilves, Q. Ge, P. Kumar, J. Shorenstein, S. A. Kazakov, T. L. Cuellar, M. T. McManus, M. A. Behlke, and B. H. Johnston (2012)
Nucleic Acids Res. 40, 9255-9271
   Abstract »    Full Text »    PDF »
Kinetic signatures of microRNA modes of action.
N. Morozova, A. Zinovyev, N. Nonne, L.-L. Pritchard, A. N. Gorban, and A. Harel-Bellan (2012)
RNA 18, 1635-1655
   Abstract »    Full Text »    PDF »
Differential association of microRNAs with polysomes reflects distinct strengths of interactions with their mRNA targets.
N. Molotski and Y. Soen (2012)
RNA 18, 1612-1623
   Abstract »    Full Text »    PDF »
Disease-linked microRNA-21 exhibits drastically reduced mRNA binding and silencing activity in healthy mouse liver.
J. R. Androsavich, B. N. Chau, B. Bhat, P. S. Linsley, and N. G. Walter (2012)
RNA 18, 1510-1526
   Abstract »    Full Text »    PDF »
A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication.
Y. Chen, A. Shen, P. J. Rider, Y. Yu, K. Wu, Y. Mu, Q. Hao, Y. Liu, H. Gong, Y. Zhu, et al. (2011)
FASEB J 25, 4511-4521
   Abstract »    Full Text »    PDF »
Mybl2, downregulated during colon epithelial cell maturation, is suppressed by miR-365.
M. Papetti and L. H. Augenlicht (2011)
Am J Physiol Gastrointest Liver Physiol 301, G508-G518
   Abstract »    Full Text »    PDF »
Activation of a microRNA response in trans reveals a new role for poly(A) in translational repression.
E. P. Ricci, T. Limousin, R. Soto-Rifo, R. Allison, T. Poyry, D. Decimo, R. J. Jackson, and T. Ohlmann (2011)
Nucleic Acids Res. 39, 5215-5231
   Abstract »    Full Text »    PDF »
Masking the 5' terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex.
E. S. Machlin, P. Sarnow, and S. M. Sagan (2011)
PNAS 108, 3193-3198
   Abstract »    Full Text »    PDF »
miR-99 Family of MicroRNAs Suppresses the Expression of Prostate-Specific Antigen and Prostate Cancer Cell Proliferation.
D. Sun, Y. S. Lee, A. Malhotra, H. K. Kim, M. Matecic, C. Evans, R. V. Jensen, C. A. Moskaluk, and A. Dutta (2011)
Cancer Res. 71, 1313-1324
   Abstract »    Full Text »    PDF »
Regulation of Heme Oxygenase-1 Protein Expression by miR-377 in Combination with miR-217.
J. D. Beckman, C. Chen, J. Nguyen, V. Thayanithy, S. Subramanian, C. J. Steer, and G. M. Vercellotti (2011)
J. Biol. Chem. 286, 3194-3202
   Abstract »    Full Text »    PDF »
The GW/WG repeats of Drosophila GW182 function as effector motifs for miRNA-mediated repression.
M. Chekulaeva, R. Parker, and W. Filipowicz (2010)
Nucleic Acids Res. 38, 6673-6683
   Abstract »    Full Text »    PDF »
Expression of miR-196b is not exclusively MLL-driven but is especially linked to activation of HOXA genes in pediatric acute lymphoblastic leukemia.
D. Schotte, E. A. M. Lange-Turenhout, D. J. P. M. Stumpel, R. W. Stam, J. G. C. A. M. Buijs-Gladdines, J. P. P. Meijerink, R. Pieters, and M. L. Den Boer (2010)
Haematologica 95, 1675-1682
   Abstract »    Full Text »    PDF »
TIMP3: a physiological regulator of adult myogenesis.
H. Liu, S.-E. Chen, B. Jin, J. A. Carson, A. Niu, W. Durham, J.-Y. Lai, and Y.-P. Li (2010)
J. Cell Sci. 123, 2914-2921
   Abstract »    Full Text »    PDF »
Systemic miRNA-195 Differentiates Breast Cancer from Other Malignancies and Is a Potential Biomarker for Detecting Noninvasive and Early Stage Disease.
H. M. Heneghan, N. Miller, R. Kelly, J. Newell, and M. J. Kerin (2010)
Oncologist 15, 673-682
   Abstract »    Full Text »    PDF »
MicroRNA-370 controls the expression of MicroRNA-122 and Cpt1{alpha} and affects lipid metabolism.
D. Iliopoulos, K. Drosatos, Y. Hiyama, I. J. Goldberg, and V. I. Zannis (2010)
J. Lipid Res. 51, 1513-1523
   Abstract »    Full Text »    PDF »
Stimulation of Inducible Nitric Oxide by Hepatitis B Virus Transactivator Protein HBx Requires MTA1 Coregulator.
T. M. Bui-Nguyen, S. B. Pakala, D. R. Sirigiri, E. Martin, F. Murad, and R. Kumar (2010)
J. Biol. Chem. 285, 6980-6986
   Abstract »    Full Text »    PDF »
Sequence context outside the target region influences the effectiveness of miR-223 target sites in the RhoB 3'UTR.
G. Sun, H. Li, and J. J. Rossi (2010)
Nucleic Acids Res. 38, 239-252
   Abstract »    Full Text »    PDF »
Modulation of Hepatitis C Virus RNA Abundance and the Isoprenoid Biosynthesis Pathway by MicroRNA miR-122 Involves Distinct Mechanisms.
K. L. Norman and P. Sarnow (2010)
J. Virol. 84, 666-670
   Abstract »    Full Text »    PDF »
MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection.
Y. Lu, Y. Zhang, H. Shan, Z. Pan, X. Li, B. Li, C. Xu, B. Zhang, F. Zhang, D. Dong, et al. (2009)
Cardiovasc Res 84, 434-441
   Abstract »    Full Text »    PDF »
Evidence of MyomiR network regulation of {beta}-myosin heavy chain gene expression during skeletal muscle atrophy.
J. J. McCarthy, K. A. Esser, C. A. Peterson, and E. E. Dupont-Versteegden (2009)
Physiol Genomics 39, 219-226
   Abstract »    Full Text »    PDF »
MicroRNA-661, a c/EBP{alpha} Target, Inhibits Metastatic Tumor Antigen 1 and Regulates Its Functions.
S. D. N. Reddy, S. B. Pakala, K. Ohshiro, S. K. Rayala, and R. Kumar (2009)
Cancer Res. 69, 5639-5642
   Abstract »    Full Text »    PDF »
An expanded seed sequence definition accounts for full regulation of the hid 3' UTR by bantam miRNA.
A. Nahvi, C. J. Shoemaker, and R. Green (2009)
RNA 15, 814-822
   Abstract »    Full Text »    PDF »
MicroRNA in the ovary and female reproductive tract.
M. Z. Carletti and L. K. Christenson (2009)
J Anim Sci 87, E29-E38
   Abstract »    Full Text »    PDF »
Activation of Pattern Recognition Receptor-Mediated Innate Immunity Inhibits the Replication of Hepatitis B Virus in Human Hepatocyte-Derived Cells.
H. Guo, D. Jiang, D. Ma, J. Chang, A. M. Dougherty, A. Cuconati, T. M. Block, and J.-T. Guo (2009)
J. Virol. 83, 847-858
   Abstract »    Full Text »    PDF »
Coordinated Changes in mRNA Turnover, Translation, and RNA Processing Bodies in Bronchial Epithelial Cells following Inflammatory Stimulation.
Y. Zhai, Z. Zhong, C.-Y. A. Chen, Z. Xia, L. Song, M. R. Blackburn, and A.-B. Shyu (2008)
Mol. Cell. Biol. 28, 7414-7426
   Abstract »    Full Text »    PDF »
Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells.
D. Zheng, N. Ezzeddine, C.-Y. A. Chen, W. Zhu, X. He, and A.-B. Shyu (2008)
J. Cell Biol. 182, 89-101
   Abstract »    Full Text »    PDF »
Liver-Specific MicroRNA miR-122 Enhances the Replication of Hepatitis C Virus in Nonhepatic Cells.
J. Chang, J.-T. Guo, D. Jiang, H. Guo, J. M. Taylor, and T. M. Block (2008)
J. Virol. 82, 8215-8223
   Abstract »    Full Text »    PDF »
Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies.
J. N. Savas, A. Makusky, S. Ottosen, D. Baillat, F. Then, D. Krainc, R. Shiekhattar, S. P. Markey, and N. Tanese (2008)
PNAS 105, 10820-10825
   Abstract »    Full Text »    PDF »
Computational analysis of miRNA-mediated repression of translation: Implications for models of translation initiation inhibition.
T. Nissan and R. Parker (2008)
RNA 14, 1480-1491
   Abstract »    Full Text »    PDF »
Loss of p53 synthesis in zebrafish tumors with ribosomal protein gene mutations.
A. W. MacInnes, A. Amsterdam, C. A. Whittaker, N. Hopkins, and J. A. Lees (2008)
PNAS 105, 10408-10413
   Abstract »    Full Text »    PDF »
Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis.
N. S. Sokol, P. Xu, Y.-N. Jan, and V. Ambros (2008)
Genes & Dev. 22, 1591-1596
   Abstract »    Full Text »    PDF »
MicroRNA-repressed mRNAs contain 40S but not 60S components.
B. Wang, A. Yanez, and C. D. Novina (2008)
PNAS 105, 5343-5348
   Abstract »    Full Text »    PDF »
Neutrophil-selective CD18 silencing using RNA interference in vivo.
X. Cullere, M. Lauterbach, N. Tsuboi, and T. N. Mayadas (2008)
Blood 111, 3591-3598
   Abstract »    Full Text »    PDF »
Messenger RNA regulation: to translate or to degrade.
A.-B. Shyu, M. F. Wilkinson, and A. van Hoof (2008)
EMBO J. 27, 471-481
   Abstract »    Full Text »    PDF »
MicroRNAs as Prognostic Indicators and Therapeutic Targets: Potential Effect on Breast Cancer Management.
A. J. Lowery, N. Miller, R. E. McNeill, and M. J. Kerin (2008)
Clin. Cancer Res. 14, 360-365
   Abstract »    Full Text »    PDF »
Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells.
L. B. Frankel, N. R. Christoffersen, A. Jacobsen, M. Lindow, A. Krogh, and A. H. Lund (2008)
J. Biol. Chem. 283, 1026-1033
   Abstract »    Full Text »    PDF »
3' Terminal oligo U-tract-mediated stimulation of decapping.
M.-G. Song and M. Kiledjian (2007)
RNA 13, 2356-2365
   Abstract »    Full Text »    PDF »
Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing.
A. Eulalio, J. Rehwinkel, M. Stricker, E. Huntzinger, S.-F. Yang, T. Doerks, S. Dorner, P. Bork, M. Boutros, and E. Izaurralde (2007)
Genes & Dev. 21, 2558-2570
   Abstract »    Full Text »    PDF »
MicroRNA Inhibition of Translation Initiation in Vitro by Targeting the Cap-Binding Complex eIF4F.
G. Mathonnet, M. R. Fabian, Y. V. Svitkin, A. Parsyan, L. Huck, T. Murata, S. Biffo, W. C. Merrick, E. Darzynkiewicz, R. S. Pillai, et al. (2007)
Science 317, 1764-1767
   Abstract »    Full Text »    PDF »
Isolation of microRNA targets by miRNP immunopurification.
G. Easow, A. A. Teleman, and S. M. Cohen (2007)
RNA 13, 1198-1204
   Abstract »    Full Text »    PDF »
Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system.
M. Wakiyama, K. Takimoto, O. Ohara, and S. Yokoyama (2007)
Genes & Dev. 21, 1857-1862
   Abstract »    Full Text »    PDF »
Inhibition of the Alpha/Beta Interferon Response by Mouse Hepatitis Virus at Multiple Levels.
J. K. Roth-Cross, L. Martinez-Sobrido, E. P. Scott, A. Garcia-Sastre, and S. R. Weiss (2007)
J. Virol. 81, 7189-7199
   Abstract »    Full Text »    PDF »
Micromanagement During the Innate Immune Response.
J. E. Dahlberg and E. Lund (2007)
Sci. STKE 2007, pe25
   Abstract »    Full Text »    PDF »
The role of GW/P-bodies in RNA processing and silencing.
A. Jakymiw, K. M. Pauley, S. Li, K. Ikeda, S. Lian, T. Eystathioy, M. Satoh, M. J. Fritzler, and E. K. L. Chan (2007)
J. Cell Sci. 120, 1317-1323
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882