Abstract
Heart disease is the number one killer in the USA, making cardiogenesis and its related pathways a relevant area of study for improving health and life expectancy. The Mexican salamander (axolotl), Ambystoma mexicanum, provides an excellent vertebrate animal model for studying myofibrillogenesis due to its naturally occurring cardiac nonfunction mutation. Homozygous recessive embryos do not develop normal hearts due to a lack of myofibril formation. In previous studies, myofibril-inducing ribonucleic acid (MIR) from the normal wild-type axolotl genome was found to rescue mutant nonfunctioning hearts through restoration of tropomyosin levels followed by normal myofibril formation. Our purpose in this study is to identify and characterize functional homologs for the MIR from human fetal heart ribonucleic acid (RNA). After randomized cloning of human fetal heart RNA, 396 clones were analyzed for rescuing ability by using mutant heart rescue bioassays and confocal microscopy. By these analyses, we discovered a functional homolog of MIR from human fetal heart RNA, which is associated with the mitochondrial cytochrome c oxidase subunit II gene. This RNA came from our clone #30 and induces tropomyosin synthesis and myofibrillogenesis in mutant axolotl hearts which ordinarily do not synthesize tropomyosin or form organized myofibrils. Clone #30, a mitochondrial RNA molecule associated with human cytochrome c oxidase, serves as a functional homolog of MIR, leading to tropomyosin production, organized myofibrils, and beating cardiac tissue in mutant hearts. These findings hold great potential for the treatment and repair of damaged hearts in patients who have suffered from myocardial infarctions and other heart diseases.
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Acknowledgments
This research was made possible through grants funded by the American Heart Association (AHA) and the National Institutes of Health (NIH grants HL61246 and HL58435), and in part, by a National Science Foundation (NSF grant NSFRUI1121151) awarded to Dr. Larry Lemanski. We are grateful to Ms. Adenike Ogunpeju, Ms. Cheryl Strube, Ms. Mallory Dennie, and Ms. Sharon Lemanski for excellent secretarial and administrative assistance in the preparation of this manuscript for publication.
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Moses-Arms, A., Kochegarov, A., Arms, J. et al. Identification of a human mitochondrial RNA that promotes tropomyosin synthesis and myocardial differentiation. In Vitro Cell.Dev.Biol.-Animal 51, 273–280 (2015). https://doi.org/10.1007/s11626-014-9834-2
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DOI: https://doi.org/10.1007/s11626-014-9834-2