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Micropeptide regulates muscle performance

It is becoming increasingly recognized that some transcripts annotated as long noncoding RNAs (lncRNAs) contain short ORFs that encode functional proteins. Eric Olson and colleagues now report the discovery and functional characterization of a micropeptide, termed myoregulin, that is translated from an annotated lncRNA and that alters the contractile properties of skeletal muscle (Cell doi:10.1016/j.cell.2015.01.009; 28 January 2015). The authors show that this 46-residue peptide is expressed specifically in skeletal muscle and has structural similarity to phospholamban and sarcolipin, two proteins that interact with the calcium pump SERCA in the sarcoplasmic reticulum of striated muscle cells and inhibit its pump activity. They further show that myoregulin colocalizes with the skeletal muscle–specific SERCA1 protein in the sarcoplasmic reticulum membrane and inhibits calcium reuptake, similarly to phospholamban and sarcolipin. They subsequently engineered mice lacking myoregulin function and found that these mice exhibited increased muscle performance on a running endurance test. The partially overlapping expression patterns of phospholamban, sarcolipin and myoregulin suggest that this family of proteins contributes to the unique contractile properties of different striated muscle types.

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Vogan, K. Micropeptide regulates muscle performance. Nat Genet 47, 198 (2015). https://doi.org/10.1038/ng.3235

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