Grifone Raphaëlle, Xie Xin, Bourgeois Adeline, Saquet Audrey, Duprez Delphine, Shi De-Li
Sorbonne Universités, UPMC Univ Paris 06, UMR 7622, Laboratory of Developmental Biology, Paris F-75005, France; CNRS, UMR 7622, Laboratory of Developmental Biology, Paris F-75005, France.
Sorbonne Universités, UPMC Univ Paris 06, UMR 7622, Laboratory of Developmental Biology, Paris F-75005, France; CNRS, UMR 7622, Laboratory of Developmental Biology, Paris F-75005, France.
Mech Dev. 2014 Nov;134:1-15. doi: 10.1016/j.mod.2014.08.003. Epub 2014 Sep 16.
RNA-binding proteins (RBP) contribute to gene regulation through post-transcriptional events. Despite the important roles demonstrated for several RBP in regulating skeletal myogenesis in vitro, very few RBP coding genes have been characterized during skeletal myogenesis in vertebrate embryo. In the present study we report that Rbm24, which encodes the RNA-binding motif protein 24, is required for skeletal muscle differentiation in vivo. We show that Rbm24 transcripts are expressed at all sites of skeletal muscle formation during embryogenesis of different vertebrates, including axial, limb and head muscles. Interestingly, we find that Rbm24 protein starts to accumulate in MyoD-positive myoblasts and is transiently expressed at the onset of muscle cell differentiation. It accumulates in myotomal and limb myogenic cells, but not in Pax3-positive progenitor cells. Rbm24 expression is under the direct regulation by MyoD, as demonstrated by in vivo chromatin immunoprecipitation assay. Using morpholino knockdown approach, we further show that Rbm24 is required for somitic myogenic progenitor cells to differentiate into muscle cells during chick somitic myogenesis. Altogether, these results highlight Rbm24 as a novel key regulator of the myogenic differentiation program during vertebrate development.
RNA结合蛋白(RBP)通过转录后事件参与基因调控。尽管已有研究表明多种RBP在体外调节骨骼肌生成中发挥重要作用,但在脊椎动物胚胎的骨骼肌生成过程中,很少有RBP编码基因得到表征。在本研究中,我们报告编码RNA结合基序蛋白24的Rbm24在体内骨骼肌分化中是必需的。我们发现,在不同脊椎动物胚胎发育过程中,Rbm24转录本在骨骼肌形成的所有部位均有表达,包括轴肌、肢体肌和头部肌肉。有趣的是,我们发现Rbm24蛋白开始在MyoD阳性成肌细胞中积累,并在肌肉细胞分化开始时短暂表达。它在体节和肢体成肌细胞中积累,但在Pax3阳性祖细胞中不积累。体内染色质免疫沉淀分析表明,Rbm24的表达受MyoD的直接调控。使用吗啉代敲低方法,我们进一步表明,在鸡体节肌生成过程中,Rbm24是体节成肌祖细胞分化为肌肉细胞所必需的。总之,这些结果突出了Rbm24作为脊椎动物发育过程中肌源性分化程序的一个新的关键调节因子。