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对Ybx1表达的转化控制调节心脏功能,以应对体内压力过载

Eshita Varma^1,2, Jana Burghaus^1,2, Thomas Schwarzl³

¹Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Basic research in cardiology

|June 28, 2023

概括

心力衰竭涉及RNA结合蛋白. 拉巴胺氨基激酶 (mTORC1) 信号传递的机械标激活Y盒结合蛋白1 (Ybx1),通过Eef2.2通过增加蛋白质合成驱动病态生长.

科学领域:

心血管生物学心血管生物学
分子心脏病学分子心脏病学
在RNA生物学,RNA生物学.

背景情况:

RNA-蛋白相互作用对心脏功能至关重要.
通过在心力衰竭中发出信号来调节RNA结合蛋白的理解很少.
拉巴胺素激酶 (mTOR) 的机械标调节心肌细胞中的翻译.

研究的目的:

研究心力衰竭中mTOR信号传递和RNA结合蛋白之间的联系.
确定Y盒结合蛋白1 (Ybx1) 在病态心脏重塑中的作用.
阐明Ybx1调节心肌细胞生长和蛋白质合成的分子机制.

主要方法:

综合性转录组和翻译组分析.
通过Ybx1.1结合的信使RNA (mRNA) 的识别.
在心脏缩模型中的体内Ybx1枯竭研究.

主要成果:

在早期的病理重塑过程中,mTORC1信号调节Ybx1翻译,独立于mRNA水平.
通过调节蛋白质合成,Ybx1对于病态心肌细胞生长至关重要.
Ybx1结合并调节了真核延长因子2 (Eef2) mRNA的翻译,促进了全球蛋白质翻译和病态生长.
在病理性心脏缩期间,Ybx1的枯竭可以保持心脏功能.

结论:

mTORC1激活通过Ybx1.1将病态信号与改变的基因表达联系起来.
Ybx1通过增加Eef2翻译和全球蛋白质合成来促进病态心脏缩.
针对mTORC1-Ybx1-Eef2轴可能为心力衰竭提供治疗策略.

关键词:

心脏衰竭是因为心脏衰竭.RNA结合蛋白质是RNA结合的蛋白质.在YBX1上,YBX1在YBX1上在mTOROR中使用mTOR.

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