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RNA 结合蛋白作为心血管疾病效应因子和调节因子的新作用。

Emerging roles for RNA-binding proteins as effectors and regulators of cardiovascular disease.

机构信息

Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.

Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2300RC, The Netherlands.

出版信息

Eur Heart J. 2017 May 7;38(18):1380-1388. doi: 10.1093/eurheartj/ehw567.

Abstract

The cardiovascular system comprises multiple cell types that possess the capacity to modulate their phenotype in response to acute or chronic injury. Transcriptional and post-transcriptional mechanisms play a key role in the regulation of remodelling and regenerative responses to damaged cardiovascular tissues. Simultaneously, insufficient regulation of cellular phenotype is tightly coupled with the persistence and exacerbation of cardiovascular disease. Recently, RNA-binding proteins such as Quaking, HuR, Muscleblind, and SRSF1 have emerged as pivotal regulators of these functional adaptations in the cardiovascular system by guiding a wide-ranging number of post-transcriptional events that dramatically impact RNA fate, including alternative splicing, stability, localization and translation. Moreover, homozygous disruption of RNA-binding protein genes is commonly associated with cardiac- and/or vascular complications. Here, we summarize the current knowledge on the versatile role of RNA-binding proteins in regulating the transcriptome during phenotype switching in cardiovascular health and disease. We also detail existing and potential DNA- and RNA-based therapeutic approaches that could impact the treatment of cardiovascular disease in the future.

摘要

心血管系统由多种细胞类型组成,这些细胞类型具有响应急性或慢性损伤调节其表型的能力。转录和转录后机制在调节受损心血管组织的重塑和再生反应中起着关键作用。同时,细胞表型调节不足与心血管疾病的持续和恶化密切相关。最近,RNA 结合蛋白(如 Quaking、HuR、Muscleblind 和 SRSF1)已成为心血管系统这些功能适应性的关键调节因子,通过指导广泛的转录后事件来显著影响 RNA 的命运,包括可变剪接、稳定性、定位和翻译。此外,RNA 结合蛋白基因的纯合缺失通常与心脏和/或血管并发症有关。在这里,我们总结了 RNA 结合蛋白在调节心血管健康和疾病中表型转换过程中的转录组的多功能作用的最新知识。我们还详细介绍了现有的和潜在的基于 DNA 和 RNA 的治疗方法,这些方法可能会影响未来心血管疾病的治疗。

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