title: A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle.
abstract: 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.
authors.affiliation: 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.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Nelson
authors.affiliation: 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.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Makarewich
authors.affiliation: 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.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Anderson
authors.affiliation: 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.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Winders
authors.affiliation: 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.
authors.forename: Constantine D
authors.initials: CD
authors.lastname: Troupes
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Austin L
authors.initials: AL
authors.lastname: Reese
authors.affiliation: 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.
authors.forename: John R
authors.initials: JR
authors.lastname: McAnally
authors.affiliation: 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.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cannon
authors.affiliation: 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.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
authors.affiliation: 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.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.affiliation: 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.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D014158:Transcription, Genetic; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D009124:Muscle Proteins; D010455:Peptides; D011510:Proteolipids; D062085:RNA, Long Noncoding; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C000604949:DWORF peptide, human; C000604950:DWORF peptide, mouse; C000596641:myoregulin, mouse; C077258:sarcolipin
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