基因敲除
生物
细胞生物学
信使核糖核酸
心功能曲线
压力过载
功能(生物学)
心力衰竭
基因表达
肌肉肥大
癌症研究
基因
内科学
内分泌学
遗传学
心肌肥大
医学
作者
Vivien Kmietczyk,J. Oelschläger,Parul Gupta,Elly Varma,S. Hartl,Jennifer Furkel,Mathias Konstandin,Alexander Marx,Zoe Loewenthal,Verena Kamuf-Schenk,Lonny Jürgensen,Christopher Stroh,Agnieszka Górska,Abel Martín-Garrido,Joerg Heineke,Tobias Jakobi,Norbert Frey,Mirko Völkers
标识
DOI:10.1016/j.yjmcc.2023.06.001
摘要
m6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytes in vivo leads to mild cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. Similarly, in vitro the knockdown of Ythdf2 results in cardiomyocyte growth and remodeling. Mechanistically, we identified the eucaryotic elongation factor 2 as post-transcriptionally regulated by Ythdf2 using cell type specific Ribo-seq data. Our study expands our understanding on the regulatory functions of m6A methylation in cardiomyocytes and how cardiac function is controlled by the m6A reader protein Ythdf2.
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