Open Access
Science, volume 351, issue 6270, pages 271-275
A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle
Nelson Benjamin R
1, 2
,
Makarewich Catherine A.
1, 2
,
ANDERSON DOUGLAS M.
1, 2
,
Winders Benjamin R
1, 2
,
Troupes Constantine D.
3, 4
,
Wu Fenfen
5
,
Reese Austin L
6, 7
,
McAnally John R
1, 2
,
Chen Xiongwen
3, 4
,
Kavalali Ege T.
6, 7
,
Cannon Stephen C.
5
,
Houser Steven R.
3, 4
,
Bassel-Duby Rhonda
1, 2
,
Olson Eric N.
1, 2
1
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
|
2
Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
|
3
Department of Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
|
4
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
|
5
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
|
6
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
|
7
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
|
Publication type: Journal Article
Publication date: 2016-01-15
PubMed ID:
26816378
Multidisciplinary
Abstract
Another micropeptide flexes its muscle Genome annotation is a complex but imperfect art. Attesting to its limitations is the growing evidence that certain transcripts annotated as long noncoding RNAs (lncRNAs) in fact code for small peptides with biologically important functions. One such lncRNA-derived micropeptide in mammals is myoregulin, which reduces muscle performance by inhibiting the activity of a key calcium pump. Nelson et al. describe the opposite activity in a second lncRNA-derived micropeptide in mammalian muscle, called DWORF (see the Perspective by Payre and Desplan). This peptide enhances muscle performance by activating the same calcium pump. DWORF may prove to be useful in improving the cardiac muscle function of mammals with heart disease. Science, this issue p. 271; see also p. 226 A long noncoding RNA encodes a small peptide that activates a calcium pump regulating muscle contraction. [Also see Perspective by Payre and Desplan] 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.
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Nelson B. R. et al. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle // Science. 2016. Vol. 351. No. 6270. pp. 271-275.
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Nelson B. R., Makarewich C. A., ANDERSON D. M., Winders B. R., Troupes C. D., Wu F., Reese A. L., McAnally J. R., Chen X., Kavalali E. T., Cannon S. C., Houser S. R., Bassel-Duby R., Olson E. N. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle // Science. 2016. Vol. 351. No. 6270. pp. 271-275.
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TY - JOUR
DO - 10.1126/science.aad4076
UR - https://doi.org/10.1126%2Fscience.aad4076
TI - A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle
T2 - Science
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
DA - 2016/01/15 00:00:00
PB - American Association for the Advancement of Science (AAAS)
SP - 271-275
IS - 6270
VL - 351
PMID - 26816378
SN - 0036-8075
SN - 1095-9203
ER -
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@article{2016_Nelson,
author = {Benjamin R Nelson and Catherine A. Makarewich and DOUGLAS M. ANDERSON and Benjamin R Winders and Constantine D. Troupes and Fenfen Wu and Austin L Reese and John R McAnally and Xiongwen Chen and Ege T. Kavalali and Stephen C. Cannon and Steven R. Houser and Rhonda Bassel-Duby and Eric N. Olson},
title = {A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle},
journal = {Science},
year = {2016},
volume = {351},
publisher = {American Association for the Advancement of Science (AAAS)},
month = {jan},
url = {https://doi.org/10.1126%2Fscience.aad4076},
number = {6270},
pages = {271--275},
doi = {10.1126/science.aad4076}
}
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Nelson, Benjamin R., et al. “A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle.” Science, vol. 351, no. 6270, Jan. 2016, pp. 271-275. https://doi.org/10.1126%2Fscience.aad4076.