Key Points
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More than 98% of the human genome is transcribed into RNA transcripts that have no or low protein coding potential; long noncoding RNAs (lncRNAS) are important epigenetic regulators of gene expression
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LncRNAs interact with components of the cellular machinery, including protein, DNA, RNA and chromatin remodelling complexes, to regulate the expression of target genes
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LncRNAs are crucial for heart development; they also have a role in cardiac diseases, such as heart failure, myocardial infarction and processes such as cardiac contractility and autophagy
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New research suggests that lncRNAs participate in renal processes and have pathogenic roles in kidney diseases
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Animal studies have linked lncRNAs to diabetic nephropathy, glomerular disease, acute renal allograft rejection, renal cell carcinoma, acute kidney injury and hypertension
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Expression of lncRNAs can be modulated, suggesting novel therapeutic avenues for the treatment of cardiac and kidney diseases
Abstract
Transcription of a large part of the human genome results in RNA transcripts that have limited or no protein-coding potential. These include long noncoding RNAs (lncRNAs), which are defined as being ≥200 nucleotides long. Unlike microRNAs, which have been extensively studied, little is known about the functional role of lncRNAs. However, studies over the past 5 years have shown that lncRNAs interfere with tissue homeostasis and have a role in pathological processes, including in the kidney and heart. The developmental expression of the microRNA sponge H19, for example, is altered in the kidneys of embryos carried by hyperglycaemic mothers, and the lncRNA Malat1 regulates hyperglycaemia-induced inflammation in endothelial cells. Putative roles for other lncRNAs have been identified in conditions such as heart failure, cardiac autophagy, hypertension, acute kidney injury, glomerular diseases, acute allograft rejection and renal cell carcinoma. This Review outlines our current understanding of the role and function of lncRNAs in kidney and cardiovascular disease as novel important regulators and potential therapeutic entry points of disease progression.
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Acknowledgements
The authors' work is supported by a grant from the Deutsche Forschungsgemeinschaft (DFG LO 1736/1-1 to J.M.L. and T.T.), a Memorial scholarship from the Else Kröner-Fresenius foundation (to J.M.L.) and by the Integrated Research and Treatment Center Transplantation of the Hannover Medical School, as well as by the EU-funded ERC Consolidator grant Longheart (to T.T.) and the Leducq-Fondation funded network Mirvad (to T.T.).
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J.M.L. researched the data and wrote the article. T.T. contributed substantially to the discussion of the content. Both authors reviewed and/or edited the manuscript before submission.
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Both authors have filed patents on the diagnostic and therapeutic use of non-coding RNAs.
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Lorenzen, J., Thum, T. Long noncoding RNAs in kidney and cardiovascular diseases. Nat Rev Nephrol 12, 360–373 (2016). https://doi.org/10.1038/nrneph.2016.51
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DOI: https://doi.org/10.1038/nrneph.2016.51
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