Cmarr/miR-540-3p axis promotes cardiomyocyte maturation transition by orchestrating Dtna expression

Here, our study showed that a heart-rich lncRNA, Cmarr, which is specifically upregulated during heart development, promoted the maturation transition of ESC-CMs. Cmarr interacted with miR-540-3p to increase the expression of Dtna (a key component of DGC), thus served as a new regulator of the DGC-YAP complex and cardiomyocyte maturation. Our study further identified that Cmarr could recover Dtna expression in the MI heart and attenuate the cardiac remodeling. RNA-seq and miRNA-seq of heart tissues本研究结果显示，一种心脏富集型长链非编码RNA（long non-coding RNA，lncRNA）Cmarr在心脏发育过程中特异性上调，可促进胚胎干细胞来源心肌细胞（ESC-CMs）的成熟转化。Cmarr可与微小RNA-540-3p（miR-540-3p）结合，上调肌营养不良蛋白（Dtna）——肌营养不良蛋白聚糖复合物（DGC）的关键组分——的表达，因此可作为DGC-YAP复合物与心肌细胞成熟的新型调控因子。本研究进一步证实，Cmarr可恢复心肌梗死（MI）心脏组织中Dtna的表达，并减轻心肌重构。针对心脏组织开展了RNA测序（RNA-seq）与微小RNA测序（miRNA-seq）