The Functions of Long Non-Coding RNA during Embryonic Cardiovascular Development and Its Potential for Diagnosis and Treatment of Congenital Heart Disease

Abstract

Congenital heart disease (CHD) arises due to errors during the embryonic development of the heart, a highly regulated process involving an interplay between cell-intrinsic transcription factor expression and intercellular signalling mediated by morphogens. Emerging evidence indicates that expression of these protein-coding genes is controlled by a plethora of previously unappreciated non-coding RNAs operating in complex feedback-control circuits. In this review, we consider the contribution of long non-coding RNA (lncRNA) to embryonic cardiovascular development before discussing applications to CHD diagnostics and therapeutics. We discuss the process of lineage restriction during cardiovascular progenitor cell differentiation, as well as the subsequent patterning of the cardiogenic progenitor fields, taking as an example the regulation of NODAL signalling in left-right patterning of the heart. lncRNA are a highly versatile group. Nuclear lncRNA can target specific genomic sequences and recruit chromatin remodelling complexes. Some nuclear lncRNA are transcribed from enhancers and regulate chromatin looping. Cytoplasmic lncRNA act as endogenous competitors for micro RNA, as well as binding and sequestering signalling proteins. We discuss features of lncRNA that limit their study by conventional methodology and suggest solutions to these problems.