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A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle.
Benjamin R Nelson1, Catherine A Makarewich1, Douglas M Anderson1
1Department 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.
Science (New York, N.Y.)
|January 28, 2016
Summary
Researchers discovered a muscle-specific peptide, dwarf open reading frame (DWORF), that enhances muscle contraction by boosting SERCA pump activity. DWORF improves calcium handling and muscle function in mice.
Area of Science:
- Molecular Biology
- Muscle Physiology
Background:
- Muscle contraction relies on calcium (Ca2+) cycling.
- The sarcoplasmic reticulum (SR) and Ca2+-ATPase (SERCA) pump are crucial for Ca2+ reuptake.
Purpose of the Study:
- To identify novel regulators of SERCA activity.
- To investigate the function of a newly discovered muscle-specific peptide, DWORF.
Main Methods:
- Identified a muscle-specific long noncoding RNA encoding the DWORF peptide.
- Localized DWORF to the SR membrane.
- Studied DWORF function in mouse cardiomyocytes and slow skeletal muscle.
Main Results:
- DWORF enhances SERCA activity by displacing inhibitors like phospholamban.
- DWORF overexpression in cardiomyocytes increased Ca2+ transient amplitude and SR Ca2+ load.
- DWORF deficiency in skeletal muscle led to slower Ca2+ clearance and relaxation.
Conclusions:
- DWORF is the first known endogenous peptide to physically interact with and activate SERCA.
- DWORF represents a novel mechanism for enhancing muscle contractility and calcium handling.
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