Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
Division of Musculoskeletal Imaging, Department of Radiology, University of California San Diego School of Medicine, 200 West Arbor Drive, San Diego, California 92103, USA.
Nat Commun. 2017 Jun 1;8:15664. doi: 10.1038/ncomms15664.
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.
尽管最近的证据表明哺乳动物中存在小开放阅读框（smORF）编码的微蛋白，但它们的功能仍有待确定。骨骼肌的发育需要单核祖细胞融合形成多核肌管，这是一个关键但知之甚少的过程。在这里，我们报告了 Minion（融合的微蛋白诱导物）的鉴定，这是一个编码必需的骨骼肌特异性微蛋白的 smORF。缺乏 Minion 的成肌祖细胞正常分化，但不能形成合胞体肌管，并且 Minion 缺陷小鼠在围产期死亡，并表现出融合肌肉纤维的明显减少。Minion 的融合活性在人类同源物中保守，并且 Minion 和跨膜蛋白 Myomaker 的共表达足以诱导细胞融合，伴随着快速的细胞骨架重排，即使在非肌肉细胞中也是如此。这些发现确立了 Minion 作为一种新型的微蛋白，是肌肉发育所必需的，并定义了一个用于诱导哺乳动物细胞融合的双组分程序。此外，这些数据还显著扩展了 smORF 编码的微蛋白的已知功能。
