Publication Date:
2016-01-28
Description:
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 delayed Ca(2+) 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- AR-063182/AR/NIAMS NIH HHS/ -- DK-099653/DK/NIDDK NIH HHS/ -- F30AR 067094/AR/NIAMS NIH HHS/ -- HL-077439,/HL/NHLBI NIH HHS/ -- HL-093039/HL/NHLBI NIH HHS/ -- HL-111665/HL/NHLBI NIH HHS/ -- R01 AR063182/AR/NIAMS NIH HHS/ -- U01-HL-100401/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):271-5. doi: 10.1126/science.aad4076.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA. Department of Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA. ; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. eric.olson@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816378" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium-Binding Proteins/metabolism
;
Humans
;
Mice
;
Mice, Knockout
;
*Muscle Contraction
;
Muscle Proteins/metabolism
;
Muscle, Skeletal/*metabolism
;
Myocardial Contraction
;
Myocytes, Cardiac/*metabolism
;
Peptides/genetics/*metabolism
;
Proteolipids/metabolism
;
RNA, Long Noncoding/genetics/metabolism
;
Sarcoplasmic Reticulum/metabolism
;
Sarcoplasmic Reticulum Calcium-Transporting ATPases/*metabolism
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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