The long non-coding RNA uc.4 influences cell differentiation through the TGF-beta signaling pathway

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD. Congenital heart disease: A molecule for healthy hearts Insights into the role and function of an RNA molecule shed light on the molecular mechanisms involved in abnormal heart development. Long non-coding RNAs (lncRNAs) play vital roles in various biological processes, including the development of cancers and congenital heart disease. Lingmei Qian at the first affiliated hospital of Nanjing Medical University and co-workers in China examined the function of an lncRNA called uc.4 in both mice stemcell lines and the hearts of zebrafish, an organismcommonly used for biological modelling. Overexpression of uc.4 in the mouse cells inhibited a key signalling pathway, which in turn influenced the cells' ability to differentiate. Uc.4 overexpression in the zebrafish resulted in abnormal heart development. The findings suggest uc.4 plays a vital role in healthy heart formation, and may provide a therapeutic target for congenital heart disease.