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

Benjamin R. Nelson, Catherine A. Makarewich, Douglas M. Anderson, Benjamin R. Winders, Constantine D. Troupes, Fenfen Wu, Austin L. Reese, John R. McAnally, Xiongwen Chen, Ege T. Kavalali, Stephen C. Cannon, Steven R. Houser, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

310 Scopus citations

Abstract

Muscle contraction depends on release of Ca2+ from the sarcoplasmic reticulum (SR) and reuptake by the Ca2+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 Ca2+ transient amplitude and SR Ca2+ load while reducing the time constant of cytosolic Ca2+ decay during each cycle of contraction-relaxation. Conversely, slow skeletal muscle lacking DWORF exhibits delayed Ca2+ clearance and relaxation and reduced SERCA activity. DWORF is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility.

Original languageEnglish (US)
Pages (from-to)271-275
Number of pages5
JournalScience
Volume351
Issue number6270
DOIs
StatePublished - Jan 15 2016

ASJC Scopus subject areas

  • General

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