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Background <p>The heart is the first organ to develop during embryogenesis and its development relies on coordinated interactions between the myocardium and the embryonic epicardium (EE), the third layer of the heart derived from the proepicardium (PE). A subset of epicardial cells undergoes an epithelial-to-mesenchymal transition (EMT), invades the subepicardial space and leads to epicardial-derived cells (EPDCs) colonizing the embryonic myocardium and differentiating into multiple cardiac lineages. However, the regulatory landscape governing these processes remains incomplete. In recent years, long non-coding RNAs (lncRNAs) have emerged as key regulators of cardiac development. Previous data from our laboratory identified two murine lncRNAs, <i>Elektra</i> and <i>Alien</i>, with differential expression during the transition from the PE to the EE.</p> Methods <p>In this study, we performed a multi-omic characterization of both lncRNAs across embryonic and adult tissues. Their transcriptional regulation was evaluated through cardiogenic transcription factors analysis, while their molecular interactomes were identified via RNA pull-down (PD) and mass spectrometry (MS) assays and subsequently validated by RNA immunoprecipitation (RIP). Functional impact was analyzed through loss-of-function experiments and RT-qPCR, focusing on cell migration and EMT dynamics, evidencing distinct roles for each lncRNA.</p> Results <p><i>Elektra</i> regulated the expression of ion channel genes in the myocardium through interaction with Qki protein, while <i>Alien</i> modulates the epicardial EMT process by interacting with Wt1 and controlling EMT-related genes, including <i>Snai1</i>, <i>Snai2</i>, <i>Cdh1</i> and <i>Cdh2</i>.</p> Conclusion <p>Altogether, our findings reveal that <i>Elektra</i> and <i>Alien</i> exert important roles in cardiac development by regulating myocardial ion channel expression and epicardial EMT, respectively, supporting new insights into lncRNA-mediated regulation of heart morphogenesis in mice.</p>

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Elektra-Qki and Alien-Wt1 lncRNA-protein interaction controls myocardial ion channel expression and epicardial EMT during heart development in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月7日

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  • Sheila Caño-Carrillo,
  • Estefanía Lozano-Velasco,
  • Diego Franco

摘要

Background

The heart is the first organ to develop during embryogenesis and its development relies on coordinated interactions between the myocardium and the embryonic epicardium (EE), the third layer of the heart derived from the proepicardium (PE). A subset of epicardial cells undergoes an epithelial-to-mesenchymal transition (EMT), invades the subepicardial space and leads to epicardial-derived cells (EPDCs) colonizing the embryonic myocardium and differentiating into multiple cardiac lineages. However, the regulatory landscape governing these processes remains incomplete. In recent years, long non-coding RNAs (lncRNAs) have emerged as key regulators of cardiac development. Previous data from our laboratory identified two murine lncRNAs, Elektra and Alien, with differential expression during the transition from the PE to the EE.

Methods

In this study, we performed a multi-omic characterization of both lncRNAs across embryonic and adult tissues. Their transcriptional regulation was evaluated through cardiogenic transcription factors analysis, while their molecular interactomes were identified via RNA pull-down (PD) and mass spectrometry (MS) assays and subsequently validated by RNA immunoprecipitation (RIP). Functional impact was analyzed through loss-of-function experiments and RT-qPCR, focusing on cell migration and EMT dynamics, evidencing distinct roles for each lncRNA.

Results

Elektra regulated the expression of ion channel genes in the myocardium through interaction with Qki protein, while Alien modulates the epicardial EMT process by interacting with Wt1 and controlling EMT-related genes, including Snai1, Snai2, Cdh1 and Cdh2.

Conclusion

Altogether, our findings reveal that Elektra and Alien exert important roles in cardiac development by regulating myocardial ion channel expression and epicardial EMT, respectively, supporting new insights into lncRNA-mediated regulation of heart morphogenesis in mice.