RT Journal Article
SR Electronic
T1 The microprotein Minion controls cell fusion and muscle formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 122697
DO 10.1101/122697
A1 Qiao Zhang
A1 Ajay Vashisht
A1 Jason O’Rourke
A1 Stéphane Y. Corbel
A1 Rita Moran
A1 Angelica Romero
A1 Loren Miraglia
A1 Jia Zhang
A1 Eric Durrant
A1 Christian Schmedt
A1 Srinath C. Sampath
A1 Srihari C. Sampath
YR 2017
UL http://biorxiv.org/content/early/2017/03/31/122697.abstract
AB Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, the functional repertoire of this microproteome remains to be determined1. In skeletal muscle, proper development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process2,3. Here we report the identification of a small ORF encoding an essential skeletal muscle specific microprotein we term Minion (microprotein inducer of fusion). Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally with marked reduction in fused muscle fibers. This fusogenic activity is conserved to the human Minion ortholog, previously annotated as a long noncoding RNA. Loss-of-function studies demonstrate that Minion is the factor providing muscle specific fusogenic function for the transmembrane protein Myomaker4. Remarkably, we demonstrate that co-expression of Minion and Myomaker is sufficient to induce rapid cytoskeletal rearrangement and homogeneous cellular fusion, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component program for the induction of mammalian cell fusion, enabling both research and translational applications. Importantly, these data also significantly expand the known functions of smORF-encoded microproteins, an under-explored source of proteomic diversity.