Lionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload

Commun Biol. 2020 Aug 13;3(1):434. doi: 10.1038/s42003-020-01164-0.


Recent high-throughput approaches have revealed a vast number of transcripts with unknown functions. Many of these transcripts are long noncoding RNAs (lncRNAs), and intergenic region-derived lncRNAs are classified as long intergenic noncoding RNAs (lincRNAs). Although Myosin heavy chain 6 (Myh6) encoding primary contractile protein is down-regulated in stressed hearts, the underlying mechanisms are not fully clarified especially in terms of lincRNAs. Here, we screen upregulated lincRNAs in pressure overloaded hearts and identify a muscle-abundant lincRNA termed Lionheart. Compared with controls, deletion of the Lionheart in mice leads to decreased systolic function and a reduction in MYH6 protein levels following pressure overload. We reveal decreased MYH6 results from an interaction between Lionheart and Purine-rich element-binding protein A after pressure overload. Furthermore, human LIONHEART levels in left ventricular biopsy specimens positively correlate with cardiac systolic function. Our results demonstrate Lionheart plays a pivotal role in cardiac remodeling via regulation of MYH6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopsy
  • Dependovirus / metabolism
  • Heart / physiopathology*
  • Heart Ventricles / ultrastructure
  • Humans
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Pressure*
  • Promoter Regions, Genetic / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Rats
  • Systole / genetics*
  • Up-Regulation / genetics


  • RNA, Long Noncoding