Akerberg Alexander A, Burns Caroline E, Burns C Geoffrey
Department of Cardiology, Boston Children's Hospital, Boston, MA, 02115, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
Pediatr Cardiol. 2019 Oct;40(7):1410-1418. doi: 10.1007/s00246-019-02180-6. Epub 2019 Aug 9.
Numerous RNA-binding proteins (RBPs) are expressed in the heart, and mutations in several RBPs have been implicated in cardiovascular disease through genetic associations, animal modeling, and mechanistic studies. However, the functions of many more cardiac RBPs, and their relevance to disease states, remain to be elucidated. Recently, we have initiated studies to characterize the functions of the RBPs RBPMS and RBPMS2 in regulating myocardial biology in zebrafish and higher vertebrate species. These studies began when we learned, using an unbiased gene discovery approach, that rbpms2a and rbpms2b in zebrafish are robust markers of embryonic myocardium. This observation, which is consistent with published data, suggests that the encoded proteins are likely to be performing critical functions in regulating one or more aspects of cardiomyocyte differentiation, proliferation, survival, and/or contractility. This notion is supported by recent reports demonstrating that zebrafish embryos with disrupted Rbpms2 function exhibit gross signs of cardiac distress. Interestingly, a 20-year-old study determined that myocardial tissue from the frog, chick, and mouse also express high levels of Rbpms and/or Rbpms2, which is suggestive of evolutionary conservation of function. In this review, we will provide a historical account of how RBPMS and RBPMS2 genes were discovered, attempt to clarify some potentially confusing nomenclature, and summarize published observations that inform our ongoing studies.
许多RNA结合蛋白(RBP)在心脏中表达,通过基因关联、动物模型和机制研究,已发现几种RBP的突变与心血管疾病有关。然而,更多心脏RBP的功能及其与疾病状态的相关性仍有待阐明。最近,我们开始研究RBPMS和RBPMS2这两种RBP在斑马鱼和高等脊椎动物物种中调节心肌生物学的功能。这些研究始于我们使用无偏基因发现方法了解到斑马鱼中的rbpms2a和rbpms2b是胚胎心肌的强大标记物。这一观察结果与已发表的数据一致,表明编码的蛋白质可能在调节心肌细胞分化、增殖、存活和/或收缩性的一个或多个方面发挥关键作用。最近的报告表明,Rbpms2功能受损的斑马鱼胚胎表现出明显的心脏窘迫迹象,这支持了这一观点。有趣的是,一项20年前的研究确定,青蛙、鸡和小鼠的心肌组织也高水平表达Rbpms和/或Rbpms2,这表明功能具有进化保守性。在这篇综述中,我们将介绍RBPMS和RBPMS2基因是如何被发现的历史,试图澄清一些可能令人困惑的命名,并总结已发表的观察结果,这些结果为我们正在进行的研究提供了参考。