循环RNAcircFTO通过编码一种新型蛋白质FTO-36aaaa来促进压力过载引起的心脏缩
Rong-Rong Zhu1,2, Qi-Rong Xu3, Zhong-Yong Liu2
1Clinical School of Medicine, Jiangxi University of Chinese Medicine, Nanchang, China.
Journal of thoracic disease
|September 15, 2025
概括
循环RNAs (circRNAs) 可以编码蛋白质. 这项研究发现,circFTO产生一种蛋白质 (FTO-36aa),通过改变RNA甲基化和基因表达来驱动心脏缩.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 病理性心脏缩和心室重塑是主要的健康问题.
- 循环RNAs (circRNAs) 与心脏缩有关,但它们的蛋白质编码潜力尚不清楚.
- 研究circRNA在心肌缩中的作用至关重要.
研究的目的:
- 探索FTO基因 (circFTO) 的circRNA及其编码蛋白 (FTO-36aa) 在心肌缩中的作用.
- 确定circFTO和FTO-36aa是否有助于心脏缩病因的发生.
主要方法:
- 建立了心脏缩的横向大动脉收缩 (TAC) 诱导的小鼠模型.
- 使用了circRNA微阵列,AAV介导的基因操纵 (过度表达/敲击),质谱和双露西法酶记者分析.
- 分析了心脏功能,心肌结构,纤维化,并确定了FTO-36aa蛋白.
主要成果:
- 在TAC模型中确定了上调的circFTO,该模型是通过FTO exon splicing生成的.
- 沉默circFTO减弱TAC诱导的心脏缩.
- 发现了一种由circFTO编码的新型蛋白质FTO-36aa,它通过降解FTO,增加m6A甲基化,并通过IGF2BP2稳定高基因mRNA来促进高.
结论:
- CircFTO及其编码的FTO-36aa蛋白在心肌缩中发挥着重要作用.
- 这项研究揭示了缩性心肌细胞中circRNA转化和m6A甲基化调节的新机制.
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