Decoding the cardiac message: the 2011 Thomas W. Smith Memorial Lecture.
Decoding the cardiac message: the 2011 Thomas W. Smith Memorial Lecture.
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DOI：
10.1161/circresaha.111.256768
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发表时间：
2012-03-02
影响因子：
20.1
通讯作者：
Dorn GW 2nd
中科院分区：
文献类型：
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作者：
Dorn GW 2nd
这篇评论反映并扩展了作者在托马斯W.史密斯纪念讲座在AHA科学会议，2011年。“解码心脏信息”是指正在进行的microRNA研究的积累结果，这些研究正在改变心脏中信使RNA（mRNA）调节机制和后果的长期概念。首先，我提供了分子遗传学领域的一个简短的历史观点，触及开创性的研究，为现代分子心血管研究铺平了道路，并帮助建立了心脏mRNA调控的当前概念的基础。下面我将介绍一些有趣的细节，这些细节是关于发现和欣赏microRNA作为RNA表达和翻译的高度保守的关键调节因子的具体研究。最后，我提供了一个个人的观点，如何不可知的全基因组技术测量microRNA，其mRNA的目标，和他们的蛋白质产物可以应用于一个集成的多系统的方法来揭示microRNA的直接和间接的影响。整合下一代测序和全球蛋白质组学的实验设计有可能解决有关心脏疾病中microRNA-mRNA相互作用的未回答的问题，疾病如何改变特定microRNA的mRNA靶向，以及microRNA中的突变和多态性核苷酸变异如何影响终末器官功能和应激反应。
This review reflects and expands upon the contents of the author’s presentation at The Thomas W. Smith Memorial Lecture at AHA Scientific Sessions, 2011. “Decoding the cardiac message” refers to accumulating results from ongoing microRNA research that is altering longstanding concepts of the mechanisms for, and consequences of, messenger RNA (mRNA) regulation in the heart. First, I provide a brief historical perspective of the field of molecular genetics, touching upon seminal research that paved the way for modern molecular cardiovascular research and helped establish the foundation for current concepts of mRNA regulation in the heart. I follow with some interesting details about the specific research that led to the discovery and appreciation of microRNAs as highly conserved pivotal regulators of RNA expression and translation. Finally, I provide a personal viewpoint as to how agnostic genome-wide techniques for measuring microRNAs, their mRNA targets, and their protein products can be applied in an integrated multi-systems approach to uncover direct and indirect effects of microRNAs. Experimental designs integrating next-generation sequencing and global proteomics have the potential to address unanswered questions regarding microRNA-mRNA interactions in cardiac disease, how disease alters mRNA targeting by specific microRNAs, and how mutational and polymorphic nucleotide variation in microRNAs can affect end-organ function and stress-response.