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.

Originally published in Science Express on 22 March 2007
Science 27 April 2007:
Vol. 316. no. 5824, pp. 575 - 579
DOI: 10.1126/science.1139089
Prev | Table of Contents | Next

Research Articles

Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA

Eva van Rooij,1 Lillian B. Sutherland,1 Xiaoxia Qi,1 James A. Richardson,1,2 Joseph Hill,3 Eric N. Olson1*

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of {alpha}–myosin heavy chain ({alpha}MHC) and up-regulation of ßMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the {alpha}MHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of ßMHC in response to stress and hypothyroidism. Thus, the {alpha}MHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.

1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.
2 Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.
3 Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390–9148, USA.

* To whom correspondence should be addressed. E-mail: eric.olson{at}utsouthwestern.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
MicroRNAs as Novel Myocardial Biomarkers.
K. B. Margulies (2009)
Clin. Chem. 55, 1897-1899
   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 »
Unique MicroRNA Profile in End-stage Heart Failure Indicates Alterations in Specific Cardiovascular Signaling Networks.
S. V. Naga Prasad, Z.-H. Duan, M. K. Gupta, V. S. K. Surampudi, S. Volinia, G. A. Calin, C.-G. Liu, A. Kotwal, C. S. Moravec, R. C. Starling, et al. (2009)
J. Biol. Chem. 284, 27487-27499
   Abstract »    Full Text »    PDF »
Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms.
K. Tu, H. Yu, Y.-J. Hua, Y.-Y. Li, L. Liu, L. Xie, and Y.-X. Li (2009)
Nucleic Acids Res. 37, 5969-5980
   Abstract »    Full Text »    PDF »
MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury.
M. Xin, E. M. Small, L. B. Sutherland, X. Qi, J. McAnally, C. F. Plato, J. A. Richardson, R. Bassel-Duby, and E. N. Olson (2009)
Genes & Dev. 23, 2166-2178
   Abstract »    Full Text »    PDF »
Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure.
P. K. Rao, Y. Toyama, H. R. Chiang, S. Gupta, M. Bauer, R. Medvid, F. Reinhardt, R. Liao, M. Krieger, R. Jaenisch, et al. (2009)
Circ. Res. 105, 585-594
   Abstract »    Full Text »    PDF »
Quantitative analysis of zeptomole microRNAs based on isothermal ramification amplification.
B. Yao, J. Li, H. Huang, C. Sun, Z. Wang, Y. Fan, Q. Chang, S. Li, and J. Xi (2009)
RNA 15, 1787-1794
   Abstract »    Full Text »    PDF »
Physiological Thyroid Hormone Levels Regulate Numerous Skeletal Muscle Transcripts.
W. E. Visser, K. A. Heemstra, S. M. A. Swagemakers, Z. Ozgur, E. P. Corssmit, J. Burggraaf, W. F. J. van Ijcken, P. J. van der Spek, J. W. A. Smit, and T. J. Visser (2009)
J. Clin. Endocrinol. Metab. 94, 3487-3496
   Abstract »    Full Text »    PDF »
MicroRNA: a new frontier in kidney and blood pressure research.
M. Liang, Y. Liu, D. Mladinov, A. W. Cowley Jr., H. Trivedi, Y. Fang, X. Xu, X. Ding, and Z. Tian (2009)
Am J Physiol Renal Physiol 297, F553-F558
   Abstract »    Full Text »    PDF »
Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells.
I. K. Guttilla and B. A. White (2009)
J. Biol. Chem. 284, 23204-23216
   Abstract »    Full Text »    PDF »
MicroRNAs in Cardiovascular Biology and Heart Disease.
D. Catalucci, P. Gallo, and G. Condorelli (2009)
Circ Cardiovasc Genet 2, 402-408
   Abstract »    Full Text »    PDF »
miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy.
Z. Lin, I. Murtaza, K. Wang, J. Jiao, J. Gao, and P.-F. Li (2009)
PNAS 106, 12103-12108
   Abstract »    Full Text »    PDF »
Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy..
J. M. Bos, J. A. Towbin, and M. J. Ackerman (2009)
J. Am. Coll. Cardiol. 54, 201-211
   Abstract »    Full Text »    PDF »
MicroRNAs and Their Role in Progressive Kidney Diseases.
M. Kato, L. Arce, and R. Natarajan (2009)
Clin. J. Am. Soc. Nephrol. 4, 1255-1266
   Abstract »    Full Text »    PDF »
Labeled microRNA pull-down assay system: an experimental approach for high-throughput identification of microRNA-target mRNAs.
R.-J. Hsu, H.-J. Yang, and H.-J. Tsai (2009)
Nucleic Acids Res. 37, e77
   Abstract »    Full Text »    PDF »
Genomics, transcriptional profiling, and heart failure..
K. B. Margulies, D. P. Bednarik, and D. L. Dries (2009)
J. Am. Coll. Cardiol. 53, 1752-1759
   Abstract »    Full Text »    PDF »
MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20.
X.-P. Ren, J. Wu, X. Wang, M. A. Sartor, J. Qian, K. Jones, P. Nicolaou, T. J. Pritchard, and G.-C. Fan (2009)
Circulation 119, 2357-2366
   Abstract »    Full Text »    PDF »
In Search of Adrenocortical Stem and Progenitor Cells.
A. C. Kim, F. M. Barlaskar, J. H. Heaton, T. Else, V. R. Kelly, K. T. Krill, J. O. Scheys, D. P. Simon, A. Trovato, W.-H. Yang, et al. (2009)
Endocr. Rev. 30, 241-263
   Abstract »    Full Text »    PDF »
MicroRNAs: Regulating a Change of Heart.
K. G. Barringhaus and P. D. Zamore (2009)
Circulation 119, 2217-2224
   Full Text »    PDF »
miR-375 maintains normal pancreatic {alpha}- and {beta}-cell mass.
M. N. Poy, J. Hausser, M. Trajkovski, M. Braun, S. Collins, P. Rorsman, M. Zavolan, and M. Stoffel (2009)
PNAS 106, 5813-5818
   Abstract »    Full Text »    PDF »
Extracardiac approaches to protecting the heart.
G. Valen (2009)
Eur. J. Cardiothorac. Surg. 35, 651-657
   Abstract »    Full Text »    PDF »
MicroRNA Regulation of Cardiovascular Development.
K. R. Cordes and D. Srivastava (2009)
Circ. Res. 104, 724-732
   Abstract »    Full Text »    PDF »
Long-Term Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy.
L. Suckau, H. Fechner, E. Chemaly, S. Krohn, L. Hadri, J. Kockskamper, D. Westermann, E. Bisping, H. Ly, X. Wang, et al. (2009)
Circulation 119, 1241-1252
   Abstract »    Full Text »    PDF »
Reciprocal Regulation of Myocardial microRNAs and Messenger RNA in Human Cardiomyopathy and Reversal of the microRNA Signature by Biomechanical Support.
S. J. Matkovich, D. J. Van Booven, K. A. Youker, G. Torre-Amione, A. Diwan, W. H. Eschenbacher, L. E. Dorn, M. A. Watson, K. B. Margulies, and G. W. Dorn II (2009)
Circulation 119, 1263-1271
   Abstract »    Full Text »    PDF »
MicroRNAs As Novel Regulators of Angiogenesis.
Y. Suarez and W. C. Sessa (2009)
Circ. Res. 104, 442-454
   Abstract »    Full Text »    PDF »
In Vitro Evidence Suggests That miR-133a-mediated Regulation of Uncoupling Protein 2 (UCP2) Is an Indispensable Step in Myogenic Differentiation.
X. Chen, K. Wang, J. Chen, J. Guo, Y. Yin, X. Cai, X. Guo, G. Wang, R. Yang, L. Zhu, et al. (2009)
J. Biol. Chem. 284, 5362-5369
   Abstract »    Full Text »    PDF »
Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
A. Shkumatava, A. Stark, H. Sive, and D. P. Bartel (2009)
Genes & Dev. 23, 466-481
   Abstract »    Full Text »    PDF »
miR-133 and miR-30 Regulate Connective Tissue Growth Factor: Implications for a Role of MicroRNAs in Myocardial Matrix Remodeling.
R. F. Duisters, A. J. Tijsen, B. Schroen, J. J. Leenders, V. Lentink, I. van der Made, V. Herias, R. E. van Leeuwen, M. W. Schellings, P. Barenbrug, et al. (2009)
Circ. Res. 104, 170-178
   Abstract »    Full Text »    PDF »
MicroRNA Silencing in Primates: Towards Development of Novel Therapeutics.
A. Petri, M. Lindow, and S. Kauppinen (2009)
Cancer Res. 69, 393-395
   Abstract »    Full Text »    PDF »
microRNAs and muscle disorders.
J.-F. Chen, T. E. Callis, and D.-Z. Wang (2009)
J. Cell Sci. 122, 13-20
   Abstract »    Full Text »    PDF »
Right into the heart of microRNA-133a.
B. Meder, H. A. Katus, and W. Rottbauer (2008)
Genes & Dev. 22, 3227-3231
   Abstract »    Full Text »    PDF »
Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids.
M. J. Drummond, J. J. McCarthy, C. S. Fry, K. A. Esser, and B. B. Rasmussen (2008)
Am J Physiol Endocrinol Metab 295, E1333-E1340
   Abstract »    Full Text »    PDF »
microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart.
N. Liu, S. Bezprozvannaya, A. H. Williams, X. Qi, J. A. Richardson, R. Bassel-Duby, and E. N. Olson (2008)
Genes & Dev. 22, 3242-3254
   Abstract »    Full Text »    PDF »
The Emerging Role of MicroRNAs in Cardiac Remodeling and Heart Failure.
V. Divakaran and D. L. Mann (2008)
Circ. Res. 103, 1072-1083
   Abstract »    Full Text »    PDF »
Podocyte-Selective Deletion of Dicer Induces Proteinuria and Glomerulosclerosis.
S. Shi, L. Yu, C. Chiu, Y. Sun, J. Chen, G. Khitrov, M. Merkenschlager, L. B. Holzman, W. Zhang, P. Mundel, et al. (2008)
J. Am. Soc. Nephrol. 19, 2159-2169
   Abstract »    Full Text »    PDF »
Differences in the Incidence of Congestive Heart Failure by Ethnicity: The Multi-Ethnic Study of Atherosclerosis.
H. Bahrami, R. Kronmal, D. A. Bluemke, J. Olson, S. Shea, K. Liu, G. L. Burke, and J. A. C. Lima (2008)
Arch Intern Med 168, 2138-2145
   Abstract »    Full Text »    PDF »
Toward MicroRNA-Based Therapeutics for Heart Disease: The Sense in Antisense.
E. van Rooij, W. S. Marshall, and E. N. Olson (2008)
Circ. Res. 103, 919-928
   Abstract »    Full Text »    PDF »
Cardiac Dissonance Without Conductors: How Dicer Depletion Provokes Chaos in the Heart.
T. Thum (2008)
Circulation 118, 1524-1527
   Full Text »    PDF »
Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling.
P. A. da Costa Martins, M. Bourajjaj, M. Gladka, M. Kortland, R. J. van Oort, Y. M. Pinto, J. D. Molkentin, and L. J. De Windt (2008)
Circulation 118, 1567-1576
   Abstract »    Full Text »    PDF »
Dicer1 Is Required for Differentiation of the Mouse Male Germline.
D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore, and B. D. Harfe (2008)
Biol Reprod 79, 696-703
   Abstract »    Full Text »    PDF »
Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis.
Y. Suarez, C. Fernandez-Hernando, J. Yu, S. A. Gerber, K. D. Harrison, J. S. Pober, M. L. Iruela-Arispe, M. Merkenschlager, and W. C. Sessa (2008)
PNAS 105, 14082-14087
   Abstract »    Full Text »    PDF »
Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction Defects.
L. E. Briggs, M. Takeda, A. E. Cuadra, H. Wakimoto, M. H. Marks, A. J. Walker, T. Seki, S. P. Oh, J. T. Lu, C. Sumners, et al. (2008)
Circ. Res. 103, 580-590
   Abstract »    Full Text »    PDF »
Discordant on/off switching of gene expression in myocytes during cardiac hypertrophy in vivo.
K. Pandya, J. Cowhig, J. Brackhan, H. S. Kim, J. Hagaman, M. Rojas, C. W. Carter Jr, L. Mao, H. A. Rockman, N. Maeda, et al. (2008)
PNAS 105, 13063-13068
   Abstract »    Full Text »    PDF »
An intronic microRNA silences genes that are functionally antagonistic to its host gene.
S. Barik (2008)
Nucleic Acids Res. 36, 5232-5241
   Abstract »    Full Text »    PDF »
The DNA/RNA-Binding Protein, Translin, Binds microRNA122a and Increases Its In Vivo Stability.
Z. Yu and N. B. Hecht (2008)
J Androl 29, 572-579
   Abstract »    Full Text »    PDF »
MicroRNAs: novel regulators in cardiac development and disease.
T. Thum, D. Catalucci, and J. Bauersachs (2008)
Cardiovasc Res 79, 562-570
   Abstract »    Full Text »    PDF »
MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination.
F. Fazi and C. Nervi (2008)
Cardiovasc Res 79, 553-561
   Abstract »    Full Text »    PDF »
Control of cardiac excitability by microRNAs.
B. Yang, Y. Lu, and Z. Wang (2008)
Cardiovasc Res 79, 571-580
   Abstract »    Full Text »    PDF »
MicroRNA and cardiac pathologies.
M. V. G. Latronico, D. Catalucci, and G. Condorelli (2008)
Physiol Genomics 34, 239-242
   Abstract »    Full Text »    PDF »
Microribonucleic Acid-21 Increases Aldosterone Secretion and Proliferation in H295R Human Adrenocortical Cells.
D. G. Romero, M. W. Plonczynski, C. A. Carvajal, E. P. Gomez-Sanchez, and C. E. Gomez-Sanchez (2008)
Endocrinology 149, 2477-2483
   Abstract »    Full Text »    PDF »
MicroRNomics: a newly emerging approach for disease biology.
C. Zhang (2008)
Physiol Genomics 33, 139-147
   Abstract »    Full Text »    PDF »
Cardiac Plasticity.
J. A. Hill and E. N. Olson (2008)
N. Engl. J. Med. 358, 1370-1380
   Full Text »    PDF »
Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish.
V. P. Yin, J. M. Thomson, R. Thummel, D. R. Hyde, S. M. Hammond, and K. D. Poss (2008)
Genes & Dev. 22, 728-733
   Abstract »    Full Text »    PDF »
Dicer-dependent pathways regulate chondrocyte proliferation and differentiation.
T. Kobayashi, J. Lu, B. S. Cobb, S. J. Rodda, A. P. McMahon, E. Schipani, M. Merkenschlager, and H. M. Kronenberg (2008)
PNAS 105, 1949-1954
   Abstract »    Full Text »    PDF »
Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.
J.-F. Chen, E. P. Murchison, R. Tang, T. E. Callis, M. Tatsuguchi, Z. Deng, M. Rojas, S. M. Hammond, M. D. Schneider, C. H. Selzman, et al. (2008)
PNAS 105, 2111-2116
   Abstract »    Full Text »    PDF »
Muscling Through the microRNA World.
T. E. Callis, Z. Deng, J.-F. Chen, and D.-Z. Wang (2008)
Experimental Biology and Medicine 233, 131-138
   Abstract »    Full Text »    PDF »
Surprises of the genome and "personalized" medicine..
A. J. Marian (2008)
J. Am. Coll. Cardiol. 51, 456-458
   Full Text »    PDF »
Molecular Remodeling in Human Heart Failure.
T. P. Cappola (2008)
J. Am. Coll. Cardiol. 51, 137-138
   Full Text »    PDF »
Intergenic transcription and developmental regulation of cardiac myosin heavy chain genes.
F. Haddad, A. X. Qin, P. W. Bodell, W. Jiang, J. M. Giger, and K. M. Baldwin (2008)
Am J Physiol Heart Circ Physiol 294, H29-H40
   Abstract »    Full Text »    PDF »
Cardiac MHC gene expression: more complexity and a step forward.
J. G. Edwards (2008)
Am J Physiol Heart Circ Physiol 294, H14-H15
   Full Text »    PDF »
An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133.
N. Liu, A. H. Williams, Y. Kim, J. McAnally, S. Bezprozvannaya, L. B. Sutherland, J. A. Richardson, R. Bassel-Duby, and E. N. Olson (2007)
PNAS 104, 20844-20849
   Abstract »    Full Text »    PDF »
Emerging Role of MicroRNAs in Cardiovascular Biology.
M. V.G. Latronico, D. Catalucci, and G. Condorelli (2007)
Circ. Res. 101, 1225-1236
   Abstract »    Full Text »    PDF »
The Oncogenic microRNA-27a Targets Genes That Regulate Specificity Protein Transcription Factors and the G2-M Checkpoint in MDA-MB-231 Breast Cancer Cells.
S. U. Mertens-Talcott, S. Chintharlapalli, X. Li, and S. Safe (2007)
Cancer Res. 67, 11001-11011
   Abstract »    Full Text »    PDF »
Altered microRNA expression in human heart disease.
S. Ikeda, S. W. Kong, J. Lu, E. Bisping, H. Zhang, P. D. Allen, T. R. Golub, B. Pieske, and W. T. Pu (2007)
Physiol Genomics 31, 367-373
   Abstract »    Full Text »    PDF »
microRNAs put their signatures on the heart.
E. van Rooij and E. N. Olson (2007)
Physiol Genomics 31, 365-366
   Full Text »    PDF »
Distinctive patterns of microRNA expression in primary muscular disorders.
I. Eisenberg, A. Eran, I. Nishino, M. Moggio, C. Lamperti, A. A. Amato, H. G. Lidov, P. B. Kang, K. N. North, S. Mitrani-Rosenbaum, et al. (2007)
PNAS 104, 17016-17021
   Abstract »    Full Text »    PDF »
MicroRNA regulation of cyclooxygenase-2 during embryo implantation.
A. Chakrabarty, S. Tranguch, T. Daikoku, K. Jensen, H. Furneaux, and S. K. Dey (2007)
PNAS 104, 15144-15149
   Abstract »    Full Text »    PDF »
Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism.
M. S. Carneiro-Ramos, G. P. Diniz, J. Almeida, R. L. P. Vieira, S. V. B. Pinheiro, R. A. Santos, and M. L. M. Barreto-Chaves (2007)
J. Physiol. 583, 213-223
   Abstract »    Full Text »    PDF »
MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure.
T. Thum, P. Galuppo, C. Wolf, J. Fiedler, S. Kneitz, L. W. van Laake, P. A. Doevendans, C. L. Mummery, J. Borlak, A. Haverich, et al. (2007)
Circulation 116, 258-267
   Abstract »    Full Text »    PDF »
What lies at the interface of regenerative medicine and developmental biology?.
D. E. Ingber and M. Levin (2007)
Development 134, 2541-2547
   Abstract »    Full Text »    PDF »
Cerebellar neurodegeneration in the absence of microRNAs.
A. Schaefer, D. O'Carroll, C. L. Tan, D. Hillman, M. Sugimori, R. Llinas, and P. Greengard (2007)
J. Exp. Med. 204, 1553-1558
   Abstract »    Full Text »    PDF »
MicroRNAs and the Failing Heart.
D. L. Mann (2007)
N. Engl. J. Med. 356, 2644-2645
   Full Text »    PDF »
Resizing the Genomic Regulation of Restenosis.
T. Matsumoto and P. M. Hwang (2007)
Circ. Res. 100, 1537-1539
   Full Text »    PDF »
A Cardiac-Specific MicroRNA Causes Cardiac Hypertrophy and Fibrosis.
(2007)
Journal Watch (General) 2007, 4
   Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)