Small peptides control heart activity

Peptides from long noncoding RNAs control a muscle calcium pump [Also see Report by Nelson et al. ] A growing body of evidence shows that so-called long noncoding RNAs (lncRNAs) often produce short peptides from small open reading frames (s mORFs) ( 1 ). Whether and how smORF-encoded peptides fulfill specific functions remain poorly understood. Recent studies in flies ( 2 ) and mammals ( 3 ) have revealed that transcripts annotated as lncRNAs encode smORF peptides that bind to, and inhibit, the sarco/endoplasmic reticulum calcium adenosine triphosphatase (SERCA), an ion pump that is a key player in handling calcium in striated muscles. On page 271 of this issue, Nelson et al. ( 4 ) report that a lncRNA-encoded small peptide competes with SERCA-inhibitory peptides, thereby favoring heart contractility in mammals. These findings open new ways to understand cardiac function and pathologies, and show that smORF peptides act as versatile regulators of protein activity.