The microprotein Minion controls cell fusion and muscle formation

Qiao Zhang, Ajay A. Vashisht, Jason O’Rourke, Stéphane Y Corbel, Rita Moran, Angelica Romero, Loren Miraglia, Jia Zhang, Eric Durrant, Christian Schmedt, Srinath C. Sampath () and Srihari C. Sampath ()
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Qiao Zhang: Genomics Institute of the Novartis Research Foundation
Ajay A. Vashisht: Genomics Institute of the Novartis Research Foundation
Jason O’Rourke: Genomics Institute of the Novartis Research Foundation
Stéphane Y Corbel: Genomics Institute of the Novartis Research Foundation
Rita Moran: Genomics Institute of the Novartis Research Foundation
Angelica Romero: Genomics Institute of the Novartis Research Foundation
Loren Miraglia: Genomics Institute of the Novartis Research Foundation
Jia Zhang: Genomics Institute of the Novartis Research Foundation
Eric Durrant: Genomics Institute of the Novartis Research Foundation
Christian Schmedt: Genomics Institute of the Novartis Research Foundation
Srinath C. Sampath: Genomics Institute of the Novartis Research Foundation
Srihari C. Sampath: Genomics Institute of the Novartis Research Foundation

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15664

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