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 language | English (US) |
|---|---|
| Pages (from-to) | 271-275 |
| Number of pages | 5 |
| Journal | Science |
| Volume | 351 |
| Issue number | 6270 |
| DOIs | |
| State | Published - Jan 15 2016 |
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ASJC Scopus subject areas
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Cite this
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 journal › Article
}
TY - JOUR
T1 - Muscle physiology
T2 - A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle
AU - Nelson, Benjamin R.
AU - Makarewich, Catherine A.
AU - Anderson, Douglas M.
AU - Winders, Benjamin R.
AU - Troupes, Constantine D.
AU - Wu, Fenfen
AU - Reese, Austin L.
AU - McAnally, John R.
AU - Chen, Xiongwen
AU - Kavalali, Ege T.
AU - Cannon, Stephen C.
AU - Houser, Steven R.
AU - Bassel-Duby, Rhonda
AU - Olson, Eric N.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84954349046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954349046&partnerID=8YFLogxK
U2 - 10.1126/science.aad4076
DO - 10.1126/science.aad4076
M3 - Article
C2 - 26816378
AN - SCOPUS:84954349046
VL - 351
SP - 271
EP - 275
JO - Science
JF - Science
SN - 0036-8075
IS - 6270
ER -