Alzein Mohamad, Lozano-Velasco Estefanía, Hernández-Torres Francisco, García-Padilla Carlos, Domínguez Jorge N, Aránega Amelia, Franco Diego
Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, 23071 Jaen, Spain.
J Cardiovasc Dev Dis. 2021 May 14;8(5):56. doi: 10.3390/jcdd8050056.
Cardiovascular development is a complex process that starts with the formation of symmetrically located precardiac mesodermal precursors soon after gastrulation and is completed with the formation of a four-chambered heart with distinct inlet and outlet connections. Multiple transcriptional inputs are required to provide adequate regional identity to the forming atrial and ventricular chambers as well as their flanking regions; i.e., inflow tract, atrioventricular canal, and outflow tract. In this context, regional chamber identity is widely governed by regional activation of distinct T-box family members. Over the last decade, novel layers of gene regulatory mechanisms have been discovered with the identification of non-coding RNAs. microRNAs represent the most well-studied subcategory among short non-coding RNAs. In this study, we sought to investigate the functional role of distinct microRNAs that are predicted to target T-box family members. Our data demonstrated a highly dynamic expression of distinct microRNAs and T-box family members during cardiogenesis, revealing a relatively large subset of complementary and similar microRNA-mRNA expression profiles. Over-expression analyses demonstrated that a given microRNA can distinctly regulate the same T-box family member in distinct cardiac regions and within distinct temporal frameworks, supporting the notion of indirect regulatory mechanisms, and dual luciferase assays on , and 3' UTR further supported this notion. Overall, our data demonstrated a highly dynamic microRNA and T-box family members expression during cardiogenesis and supported the notion that such microRNAs indirectly regulate the T-box family members in a tissue- and time-dependent manner.
心血管发育是一个复杂的过程，始于原肠胚形成后不久对称分布的心脏中胚层前体的形成，并以具有不同入口和出口连接的四腔心脏的形成为结束。需要多种转录输入来为正在形成的心房和心室腔及其侧翼区域（即流入道、房室管和流出道）提供足够的区域特征。在这种情况下，区域腔室特征广泛地由不同T-box家族成员的区域激活所控制。在过去十年中，随着非编码RNA的鉴定，发现了新的基因调控机制层。微小RNA是短非编码RNA中研究最深入的亚类。在本研究中，我们试图研究预测靶向T-box家族成员的不同微小RNA的功能作用。我们的数据表明，在心脏发生过程中，不同的微小RNA和T-box家族成员具有高度动态的表达，揭示了互补和相似的微小RNA-信使核糖核酸表达谱的相对较大子集。过表达分析表明，给定的微小RNA可以在不同的心脏区域和不同的时间框架内对同一个T-box家族成员进行不同的调节，这支持了间接调控机制的概念，并且对、和3'非翻译区的双荧光素酶测定进一步支持了这一概念。总体而言，我们的数据表明在心脏发生过程中微小RNA和T-box家族成员具有高度动态的表达，并支持了这样的观点，即这些微小RNA以组织和时间依赖性方式间接调节T-box家族成员。
