A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle.

Autor: Nelson BR; 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., Makarewich CA; 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., Anderson DM; 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., Winders BR; 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., Troupes CD; 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., Wu F; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Reese AL; 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., McAnally JR; 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., Chen X; 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., Kavalali ET; 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., Cannon SC; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Houser SR; 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., Bassel-Duby R; 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., Olson EN; 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.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2016 Jan 15; Vol. 351 (6270), pp. 271-5.
DOI: 10.1126/science.aad4076
Abstrakt: 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.
(Copyright © 2016, American Association for the Advancement of Science.)
Databáze: MEDLINE
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