The Function and Therapeutic Potential of Long Non-coding RNAs in Cardiovascular Development and Disease

The popularization of genome-wide analyses and RNA sequencing led to the discovery that a large part of the human genome, while effectively transcribed, does not encode proteins. Long non-coding RNAs have emerged as critical regulators of gene expression in both normal and disease states. Studies of long non-coding RNAs expressed in the heart, in combination with gene association studies, revealed that these molecules are regulated during cardiovascular development and disease. Some long non-coding RNAs have been functionally implicated in cardiac pathophysiology and constitute potential therapeutic targets. Here, researchers from the Luxembourg Institute of Health discuss the current knowledge of the function of long non-coding RNAs in the cardiovascular system, with an emphasis on cardiovascular development and biology, focusing on hypertension, coronary artery disease, myocardial infarction, ischemia, and heart failure. They discuss potential therapeutic implications and the challenges of long non-coding RNA research, with directions for future research and translational focus.

Classification of lncRNAs by Mechanism of Action

Signal lncRNAs respond to specific stimuli and thus show expression specific to cell type. Decoys bind transcription factors and other proteins away from their target site, repressing transcription. Guides interact with regulatory proteins, forming ribonucleoprotein complexes, and direct them to their target sites in subcellular locations. Scaffolds serve as platforms to bring different proteins together, both in the cytoplasm and in the nucleus, activating or repressing transcription. Enhancers are regulatory sequences in which transcription factors bind to initiate transcription; these regions of the genome produce several transcripts, enhancer lncRNAs, which act in cis to regulate expression of target genes. In the cytoplasm, lncRNAs can activate or inhibit translation by binding to target mRNAs. They can also regulate protein trafficking and signaling, such as phosphorylation. Sponging miRNAs is another way lncRNAs (including circular RNAs) regulate gene expression post-transcriptionally.

Gomes CPC, Spencer H, Ford KL, Michel LYM, Baker AH, Emanueli C, Balligand JL, Devaux Y. (2017) The Function and Therapeutic Potential of Long Non-coding RNAs in Cardiovascular Development and Disease. Mol Ther Nucleic Acids 8:494-507. [article]

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