Myosin 7b is a regulatory long noncoding RNA (lncMYH7b) in the human heart

J Biol Chem. 2021 Jan-Jun:296:100694. doi: 10.1016/j.jbc.2021.100694. Epub 2021 Apr 22.


Myosin heavy chain 7b (MYH7b) is an ancient member of the myosin heavy chain motor protein family that is expressed in striated muscles. In mammalian cardiac muscle, MYH7b RNA is expressed along with two other myosin heavy chains, β-myosin heavy chain (β-MyHC) and α-myosin heavy chain (α-MyHC). However, unlike β-MyHC and α-MyHC, which are maintained in a careful balance at the protein level, the MYH7b locus does not produce a full-length protein in the heart due to a posttranscriptional exon-skipping mechanism that occurs in a tissue-specific manner. Whether this locus has a role in the heart beyond producing its intronic microRNA, miR-499, was unclear. Using cardiomyocytes derived from human induced pluripotent stem cells as a model system, we found that the noncoding exon-skipped RNA (lncMYH7b) affects the transcriptional landscape of human cardiomyocytes, independent of miR-499. Specifically, lncMYH7b regulates the ratio of β-MyHC to α-MyHC, which is crucial for cardiac contractility. We also found that lncMYH7b regulates beat rate and sarcomere formation in cardiomyocytes. This regulation is likely achieved through control of a member of the TEA domain transcription factor family (TEAD3, which is known to regulate β-MyHC). Therefore, we conclude that this ancient gene has been repurposed by alternative splicing to produce a regulatory long-noncoding RNA in the human heart that affects cardiac myosin composition.

Keywords: alternative splicing; gene regulation; heart failure; long noncoding RNA (lncRNA); myosin heavy chain (MyHC); myosin heavy chain 7b (MYH7b).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiac Myosins / chemistry
  • Cardiac Myosins / metabolism*
  • Humans
  • Induced Pluripotent Stem Cells
  • MicroRNAs / genetics
  • Molecular Dynamics Simulation
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocytes, Cardiac / metabolism
  • Myosin Heavy Chains / chemistry
  • Myosin Heavy Chains / metabolism*
  • Protein Conformation
  • RNA, Long Noncoding / genetics*


  • MIRN499 microRNA, human
  • MYH7 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Cardiac Myosins
  • Myosin Heavy Chains