Transforming Principles: MicroRNAs in Muscle and Cardiac Development
Posted May 12, 2009
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Overview
MicroRNAs are short pieces of RNA that can bind complementary sequences in the transcripts of specific genes, targeting those transcripts for destruction. Until a few years ago, this type of gene regulation was thought to be a rare aberration.
Recently, though, researchers have realized that microRNAs are ubiquitous, and may regulate up to a third of all human gene expression. The ability of naturally-occurring microRNAs to regulate the expression of huge numbers of genes in eukaryotic cells, and the ease of diverting this regulatory system with short oligonucleotides, could be a tremendous boon to medicine.
At the Academy's March 20, 2009, meeting on microRNAs in cardiac and muscle development, Thomas Thum described his work on the microRNA expression patterns in cardiac tissues from healthy, failing, and fetal hearts. Maha Abdellatif discussed her group's work on ischemic preconditioning. Nicholas Sokol gave a summary of his work on neuromuscular remodeling in flies.
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Journal Articles
Thomas Thum
Thum T, Gross C, Fiedler J. 2008. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456: 980-984.
Thum T. 2008. Cardiac dissonance without conductors: how dicer depletion provokes chaos in the heart. Circulation 118: 1524-1527.
Thum T, Catalucci D, Bauersachs J. 2008. MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc. Res. 79: 562-570. Full Text
Nicholas Sokol
Sokol NS, Xu P, Jan YN, Ambros V. 2008. Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis. Genes Dev. 22: 1591-1596.
Sokol NS. 2008. An overview of the identification, detection, and functional analysis of Drosophila microRNAs. Methods Mol. Biol. 420: 319-334.
Sokol NS, Ambros V. 2005. Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. Genes Dev. 19: 2343-2354. Full Text
Maha Abdellatif
Rane S, He M, Sayed D, et al. 2009. Downregulation of MiR-199a derepresses Hypoxia-Inducible Factor-1? and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ. Res. [Epub ahead of print]
Sayed D, Rane Shweta R, Lypowy J, et al. 2008. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol. Biol. Cell 19: 3272-3282. Full Text
Sayed D, Hong C, Chen I-Y, et al. 2007. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ. Res. 100: 416-424. Full Text
Rusty Montgomery
Montgomery RL, Davis CA, Potthoff MJ, et al. 2007. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev. 21: 1790-1802 Full Text
Montgomery RL, Potthoff MJ, Haberland M, et al. 2008. Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice. J. Clin. Invest. 118: 3588-3597. Full Text
Haberland M., Montgomery RL, Olson EN. 2009. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet. 10: 32-42.
Speakers
Thomas Thum, MD, PhD
Julius-Maximilians University
e-mail | publications
Thomas Thum is a working physician who also directs the research group on cardiac wounding and healing at Julius-Maximilians University in Wurzburg, Germany. Thum received his PhD in London at the Imperial College of Medicine, and got his medical degree from the University of Hannover in Germany.
Nicholas Sokol, PhD
Indiana University
e-mail | web site | publications
Nicholas Sokol received his doctoral degree from Yale University in 2001, then spent several years as a postdoctoral fellow in Victor Ambros's laboratory at Dartmouth Medical School—the lab that discovered the first microRNAs. After his postdoctoral fellowship, Sokol moved to Indiana University in Bloomington, where he now studies the role of microRNAs in muscular development.
Maha Abdellatif, MD
University of Medicine and Dentistry of New Jersey
e-mail | web site | publications
Maha Abdellatif received her medical degree from the University of Alexandria in Egypt, then came to the United States for postdoctoral training at Baylor College of Medicine in Houston, TX. In 2001, she moved to the New York area, where she is now an associate professor at the University of Medicine and Dentistry of New Jersey (UMDNJ).
Rusty Montgomery, PhD
miRagen Therapeutics
e-mail | web site | publications
Rusty Montgomery received his PhD in genetics and development from the University of Texas Southwestern in Dallas, where he worked with Eric Olson studying the roles of class I histone deacetylases in cardiovascular development and disease. He then stayed on as a postdoctoral fellow in the Olson laboratory, investigating the biological functions of microRNAs in cardiac disease. In 2009, he joined miRagen Therapeutics, a biopharmaceutical company developing microRNA based therapeutics for cardiovascular diseases.
Alan Dove
Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.