Previous studies have shown that eukaryotic elongation factor 1A2 (eEF1A2) serves as an essential heart-specific translation elongation element and that its mutation or knockout delays heart development and causes congenital heart disease and death among species. However, the function and regulatory mechanisms of eEF1A2 in mammalian heart development remain largely unknown. Here we identified the long noncoding RNA (lncRNA) Cpmer (cytoplasmic mesoderm regulator), which interacted with eEF1A2 to co-regulate differentiation of mouse and human embryonic stem cell-derived cardiomyocytes. Mechanistically, Cpmer specifically recognized Eomes mRNA by RNA-RNA pairing and facilitated binding of eEF1A2 with Eomes mRNA, guaranteeing Eomes mRNA translation and cardiomyocyte differentiation. Our data reveal a novel functionally conserved lncRNA that can specifically regulate Eomes translation and cardiomyocyte differentiation, which broadens our understanding of the mechanism of lncRNA involvement in the subtle translational regulation of eEF1A2 during mammalian heart development.

先前的研究表明，真核生物延伸因子 1A2 (eEF1A2) 是一种必不可少的心脏特异性翻译延伸元件，其突变或敲除会延迟心脏发育并导致物种间先天性心脏病和死亡。然而，eEF1A2 在哺乳动物心脏发育中的功能和调控机制仍然很大程度上未知。在这里，我们鉴定了长链非编码 RNA (lncRNA) Cpmer（细胞质中胚层调节剂），它与 eEF1A2 相互作用，共同调节小鼠和人类胚胎干细胞衍生的心肌细胞的分化。在机制上，Cpmer通过 RNA-RNA 配对特异性识别Eomes mRNA，并促进 eEF1A2 与Eomes mRNA 的结合，保证Eomes mRNA翻译和心肌细胞分化。我们的数据揭示了一种新的功能保守的 lncRNA，它可以特异性调节Eomes翻译和心肌细胞分化，这拓宽了我们对 lncRNA 参与哺乳动物心脏发育过程中 eEF1A2 微妙翻译调控机制的理解。