Antioxid Redox Signal:中科院生物物理所姬广聚研究组等揭示RNA结合蛋
2017年3月28日，国际期刊《Antioxidants & Redox Signaling》杂志在线发表了中国科学院生物物理研究所姬广聚研究员和王会文研究员合作的一篇研究论文，论文揭示了RNA结合蛋白调控急性心肌梗死的机制。顾磊等为第一作者，姬广聚、王会文为该文的共同通讯作者。
心肌梗死是严重危害人类健康的高发性疾病，迄今缺乏有效的防治办法。因此，揭示心肌梗死的分子机制具有重要临床意义。
RNA结合蛋白CUGBP1在心脏发育中起到重要作用，然而CUGBP1在心脏疾病中的功能尚未见报道。借助急性心肌梗死(AMI)疾病模型，中国科学院生物物理研究所姬广聚课题组深入研究了CUGBP1在心肌梗死中的功能和机制。他们发现小鼠心梗心脏中CUGBP1表达显著降低，其降低的机制为AMI中RNA结合蛋白HuR由细胞核转位到细胞质，结合位于CUGBP1 3’UTR区域的ARE元件，而致CUGBP1表达降低。借助重组腺病毒表达系统，恢复AMI中降低的CUGBP1表达。CUGBP1转基因AMI小鼠促使AMI心脏功能和心肌病理损伤显著改善。这种改善得益于上调的CUGBP1促进AMI心脏中VEGF-A表达，进而促进心肌梗死区血管新生和心肌细胞抗凋亡能力。
图：CUGBP1转基因小鼠促使AMI心脏功能和心肌病理损伤显著改善
原文链接：
Reconstitution of HuR-Inhibited CUGBP1 expression Protects Cardiomyocytes from Acute Myocardial Infarction-Induced Injury
原文摘要：
Aim: Myocardial infarction (MI) is one of the leading causes of death in elderly people. Expanding the knowledge of the molecular mechanisms underlying MI is of profound importance to developing a cure for MI. The CUGBP- and ETR-3-like factor (CELF) proteins, a family of RNA-binding proteins, play key roles in RNA metabolism. To determine the functions and molecular mechanisms of CELF proteins in MI, an animal model of acute myocardial infarction (AMI) was used in our study.
Results: We found that the CUG triplet repeat RNA-binding protein 1 (CUGBP1)/CELF1 expression levels were decreased in AMI-injured hearts, and further studies showed that two highly conserved adenylate-uridylate-rich (AU-rich) elements in the 3′UTR of CUGBP1 were responsible for the decreased CUGBP1 expression. Upon AMI, human antigen R (HuR) was relocated to the cytoplasm from the nucleus and interacted with these AU-rich elements to affect the expression of CUGBP1. Reintroduction of CUGBP1 via gene delivery by recombinant adenovirus improved cardiac function in AMI mice. Our studies also indicated that CUGBP1 protected cardiomyocytes from ischemia-induced injury through the promotion of angiogenesis and inhibition of apoptosis by regulating the vascular endothelial growth factor-A gene.
Innovation and Conclusion: Our studies indicate a role for CUGBP1 in cardiac disease and reveal a novel MI post-transcriptional gene regulatory mechanism. The reconstitution of CUGBP1 could be developed as a potential therapeutic option for the management of MI. Antioxid. Redox Signal. 00, 000–000.
作者：姬广聚和王会文
