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Biochim Biophys Acta Mol Cell Res. 2018 Feb;1865(2):247-258. doi: 10.1016/j.bbamcr.2017.11.002. Epub 2017 Nov 8.

A heart-enriched antisense long non-coding RNA regulates the balance between cardiac and skeletal muscle triadin.

Author information

1
Cardiovascular Research Unit, Luxembourg Health Institute, Luxembourg.
2
Heart Failure and Transplantology Department, Institute of Cardiology, Warsaw, Poland.
3
Cardiovascular Research Unit, Luxembourg Health Institute, Luxembourg. Electronic address: yvan.devaux@lih.lu.

Abstract

Non-coding RNAs play major roles in cardiac pathophysiology. Recent studies reported that long non-coding RNAs (lncRNAs) are dysregulated in the failing heart, but how they contribute to heart failure development is unclear. In this study, we aimed to identify heart-enriched lncRNAs and investigate their regulation and function in the failing heart.

RESULTS:

Analysis of a RNA-seq dataset of 15 Caucasian tissues allowed the identification of 415 heart-enriched lncRNAs. Fifty-three lncRNAs were located on the genome in close vicinity to protein-coding genes associated with cardiac function and disease. Analysis of a second RNA-seq dataset of 16 failing human hearts highlighted one lncRNA which we arbitrarily named TRDN-AS due to its localisation in the antisense position of the gene encoding triadin (TRDN). Expression of TRDN-AS and cardiac TRDN was up-regulated in biopsies from failing human hearts compared to control hearts. In failing hearts, TRDN-AS was positively correlated with a cardiac isoform of TRDN and negatively correlated with a skeletal muscle isoform of TRDN. A murine homolog of human TRDN-AS was identified and found to be enriched in the heart and localised in the nuclear compartment of cardiomyocytes. Trdn-AS expression as well as the ratio between cardiac and skeletal muscle isoforms were down-regulated after experimental myocardial infarction. In murine cardiomyocytes, activation of Trdn-AS transcription with the CRISPR/dCas9-VPR system enhanced the ratio between cardiac and skeletal isoforms of Trdn.

CONCLUSION:

The lncRNA TRDN-AS regulates the balance between cardiac and skeletal isoforms of triadin. This finding may have implications for the treatment of heart failure.

KEYWORDS:

Cardiac disease; Gene editing; Heart; Heart failure; Long non-coding RNA; RNA sequencing; Regulation of gene expression; Transcription; Triadin

PMID:
29126880
DOI:
10.1016/j.bbamcr.2017.11.002
[Indexed for MEDLINE]

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