A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle

Muscle contraction depends on release of Ca(2+) from the sarcoplasmic reticulum (SR) and reuptake by the Ca(2+)adenosine triphosphatase SERCA. We discovered a putative muscle-specific long noncoding RNA that encodes a peptide of 34 amino acids and that we named dwarf open reading frame (DWORF). DWORF localizes to the SR membrane, where it enhances SERCA activity by displacing the SERCA inhibitors, phospholamban, sarcolipin, and myoregulin. In mice, overexpression of DWORF in cardiomyocytes increases peak Ca(2+) transient amplitude and SR Ca(2+) load while reducing the time constant of cytosolic Ca(2+) decay during each cycle of contraction-relaxation. Conversely, slow skeletal muscle lacking DWORF exhibits…

• WF
  Welch Foundation

  Award: 1-0025
• CP
  Cancer Prevention and Research Institute of Texas
• FL
  Fondation Leducq
• NI
  National Institutes of Health

  Awards: U01-HL-100401, HL-077439, AR-063182, HL-111665, HL-093039, DK-099653
• NI
  National Institute of Arthritis and Musculoskeletal and Skin Diseases