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 journalArticle

226 Citations (Scopus)

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

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Long Noncoding RNA
Open Reading Frames
Sarcoplasmic Reticulum
Muscles
Peptides
Muscle Contraction
Cardiac Myocytes
Adenosine Triphosphatases
Skeletal Muscle
Amino Acids
Membranes

ASJC Scopus subject areas

  • General

Cite this

Nelson, B. R., Makarewich, C. A., Anderson, D. M., Winders, B. R., Troupes, C. D., Wu, F., ... Olson, E. N. (2016). Muscle physiology: A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science, 351(6270), 271-275. https://doi.org/10.1126/science.aad4076

Muscle physiology : A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. / Nelson, Benjamin R.; Makarewich, Catherine A.; Anderson, Douglas M.; Winders, Benjamin R.; Troupes, Constantine D.; Wu, Fenfen; Reese, Austin L.; McAnally, John R.; Chen, Xiongwen; Kavalali, Ege T.; Cannon, Stephen C.; Houser, Steven R.; Bassel-Duby, Rhonda; Olson, Eric N.

In: Science, Vol. 351, No. 6270, 15.01.2016, p. 271-275.

Research output: Contribution to journalArticle

Nelson, BR, Makarewich, CA, Anderson, DM, Winders, BR, Troupes, CD, Wu, F, Reese, AL, McAnally, JR, Chen, X, Kavalali, ET, Cannon, SC, Houser, SR, Bassel-Duby, R & Olson, EN 2016, 'Muscle physiology: A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle', Science, vol. 351, no. 6270, pp. 271-275. https://doi.org/10.1126/science.aad4076
Nelson BR, Makarewich CA, Anderson DM, Winders BR, Troupes CD, Wu F et al. Muscle physiology: A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science. 2016 Jan 15;351(6270):271-275. https://doi.org/10.1126/science.aad4076
Nelson, Benjamin R. ; Makarewich, Catherine A. ; Anderson, Douglas M. ; Winders, Benjamin R. ; Troupes, Constantine D. ; Wu, Fenfen ; Reese, Austin L. ; McAnally, John R. ; Chen, Xiongwen ; Kavalali, Ege T. ; Cannon, Stephen C. ; Houser, Steven R. ; Bassel-Duby, Rhonda ; Olson, Eric N. / Muscle physiology : A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. In: Science. 2016 ; Vol. 351, No. 6270. pp. 271-275.
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