The microprotein Minion controls cell fusion and muscle formation

Nat Commun. 2017 Jun 1;8:15664. doi: 10.1038/ncomms15664.

Abstract

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein. Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally and demonstrate a marked reduction in fused muscle fibres. The fusogenic activity of Minion is conserved in the human orthologue, and co-expression of Minion and the transmembrane protein Myomaker is sufficient to induce cellular fusion accompanied by rapid cytoskeletal rearrangement, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component programme for the induction of mammalian cell fusion. Moreover, these data also significantly expand the known functions of smORF-encoded microproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • CRISPR-Cas Systems
  • Cell Differentiation
  • Cytoskeleton / physiology*
  • Female
  • Genotype
  • Lung / embryology
  • Male
  • Mass Spectrometry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Muscle, Skeletal / physiology*
  • Myoblasts / cytology
  • Open Reading Frames*
  • Regeneration
  • Stem Cells

Substances

  • 3' Untranslated Regions
  • Membrane Proteins
  • Mymx protein, mouse