The Functions And Mechanisms Of Long Noncoding RNA Cpmer In Cardiomyocyte Differentiation

The occurrence of congenital heart diseases due to the defects in embryonic heart development has become a major factor threatening the health of newborns worldwide.Therefore,a comprehensive understanding of the regulatory molecules and mechanisms in cardiac development is important for identifying potential targets for intervention.The proper expression of key protein-coding genes in the indicated stages is a prerequisite to ensure heart development,their deletion or mutation may cause cardiac developmental defects and diseases.These key protein-coding genes are also strictly regulated at multiple levels.Therefore,exploring the precise regulation of important transcription factors in cardiomyocyte differentiation contributes to a comprehensive understanding of the mechanisms of cardiogenesis and heart disease development.Long noncoding RNAs(lnc RNAs),as tissue-and stage-specific epigenetic regulators,have attracted extensive attention for their roles in various biological processes,including heart development.Previous studies have shown that lnc RNAs localized in the nucleus are able to regulate the epigenetic modification and transcription of the downstream genes.In addition,only about 4% of lnc RNAs are mainly enriched in the cytoplasm,they are found to participate in post-transcriptional regulation of genes by regulating m RNA stability,translation,or protein degradation processes.However,the post-transcription regulatory mechanisms of lnc RNAs during cardiomyocyte differentiation deserve further investigation.Our study identified a novel lnc RNA(cytoplasmic mesoderm regulator,Cpmer)that was specifically expressed in the heart and significantly up-regulated from mesoderm stage.Cpmer was important for cardiomyocyte differentiation and its deletion resulted in the disability of embryonic stem cells(ESCs)to differentiate into cardiomyocytes.And overexpression.Mechanistic research revealed that the cytoplasm localized Cpmer recognized the m RNA of the important mesoderm transcription factor Eomes and directly influenced its translation.The ability of Cpmer in regulating Eomes translation and cardiomyocyte differentiation depended on its combination with the heart-specific translation elongation factor e EF1A2 and recruitment of polysomes.More importantly,we identified the human homologous transcript of Cpmer,CPMER,that also bound to e EF1A2 and regulated the translation of EOMES m RNA.Thus,our study focused on revealing the subtle regulatory mechanisms of Cpmer,which was functionally conserved in human and mouse cardiomyocyte differentiation and discovered a new epigenetic mechanism of lnc RNA-mediated specific gene translation.In summary,our study identified the functionally conserved Cpmer as a novel lnc RNA capable of regulating cardiac development,and also discovered a new epigenetic mechanism of lnc RNA-mediated specific gene translation,which improved our knowledge of the precise post-transcriptional regulation of key transcription factors during cardiomyocyte differentiation.