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Review
. 2020 Jan 28;141(4):313-328.
doi: 10.1161/CIRCULATIONAHA.119.042474. Epub 2020 Jan 27.

Regulatory RNAs in Heart Failure

Clarissa Pedrosa Costa Gomes  1 , Blanche Schroen  2 , Gabriela M Kuster  3 , Emma L Robinson  2 , Kerrie Ford  4 , Iain B Squire  5 , Stephane Heymans  2 , Fabio Martelli  6 , Costanza Emanueli  4 , Yvan Devaux  1 ; EU-CardioRNA COST Action (CA17129)
Affiliations
Review

Regulatory RNAs in Heart Failure

Clarissa Pedrosa Costa Gomes et al. Circulation. .

Abstract

Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.

Keywords: RNA; biomarkers; epigenetics; heart failure; transcriptome analysis.

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Figures

Figure 1.
Figure 1.
The RNA family and regulatory RNAs. Nts indicates nucleotides.
Figure 2.
Figure 2.
Main mechanisms of action of ncRNAs. Noncoding RNAs (microRNAs, long non-coding RNAs, and circular RNAs), represented in orange, act in different ways to regulate gene expression, such as chromatinmodification, transcriptional and translational activation and repression, protein signalling, scaffold, and miRNA sponge. miRNA indicates microRNA.
Figure 3.
Figure 3.
Most frequent posttranscriptional modifications in regRNAs. Simplified chemical structure of modified RNA nitrogenous bases: purple, pseudouridine [y], reported in the three ncRNAs; pink, N6-methyladenosine [m6A] and N1-methyladenosine [m1A], observed in circRNA and lncRNA; blue, 5-methylcytosine [m5C] and adenosine to inosine editing [A to I], occuring in lncRNA and miRNA. circRNA indicates circular RNA; lncRNA, long non-coding RNA; miRNA, microRNA; and regRNA, regulatory RNA.
Figure 4.
Figure 4.
Future directions. circRNA indicates circular RNA; lncRNA, long non-coding RNA; miRNA, microRNA; and regRNA, regulatory RNA.
See this image and copyright information in PMC

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