Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames

Science. 2013 Sep 6;341(6150):1116-20. doi: 10.1126/science.1238802. Epub 2013 Aug 22.


Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism*
  • Conserved Sequence
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster
  • Evolution, Molecular
  • Ion Transport
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • Muscle, Skeletal / metabolism*
  • Myocardial Contraction*
  • Myocardium / metabolism*
  • Open Reading Frames
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / physiology*
  • Protein Structure, Secondary
  • Transaldolase / genetics
  • Transaldolase / metabolism


  • Drosophila Proteins
  • Muscle Proteins
  • Peptides
  • sarcolamban protein, Drosophila
  • Tal protein, Drosophila
  • Transaldolase
  • Calcium

Associated data

  • RefSeq/NR_001662