College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China.
Henan Key Laboratory for Innovation and Utilization of Chicken Germplasm Resources, Zhengzhou 450046, China.
J Agric Food Chem. 2024 May 29;72(21):12240-12250. doi: 10.1021/acs.jafc.4c00520. Epub 2024 May 19.
LIM domain binding 3 () serves as a striated muscle-specific Z-band alternatively spliced protein that plays an important role in mammalian skeletal muscle development, but its regulatory role and molecular mechanism in avian muscle development are still unclear. In this study, we reanalyzed RNA sequencing data sets of 1415 samples from 21 chicken tissues published in the NCBI GEO database. First, three variants (-X, -XN1, and -XN2) generated by alternative splicing of the gene were identified in chicken skeletal muscle, among which -XN1 and -XN2 are novel variants. -X and -XN1 are derived from exon skipping in chicken skeletal muscle at the E18-D7 stage and share three LIM domains, but -XN2 lacks a LIM domain. Our results preliminarily suggest that the formation of three variants of is regulated by . The three splice isomers have divergent functions in skeletal muscle according to in vitro and in vivo assays. Finally, we identified the mechanism by which different variants play different roles through interactions with and , which promote the proliferation and differentiation of chicken myoblasts, in turn regulating chicken myogenesis. In conclusion, this study revealed the divergent roles of three variants in chicken myogenesis and muscle remodeling and demonstrated their regulatory mechanism through protein-protein interactions.
LIM 结构域结合蛋白 3 () 作为一种横纹肌特异性 Z 带可变剪接蛋白,在哺乳动物骨骼肌发育中发挥重要作用,但它在禽类肌肉发育中的调节作用和分子机制尚不清楚。在本研究中,我们重新分析了 NCBI GEO 数据库中发表的 21 种鸡组织的 1415 个样本的 RNA 测序数据集。首先,在鸡骨骼肌中鉴定出基因通过可变剪接产生的三个变体 (-X、-XN1 和 -XN2),其中 -XN1 和 -XN2 是新变体。-X 和 -XN1 来源于鸡骨骼肌在 E18-D7 阶段的外显子跳跃,共享三个 LIM 结构域,但 -XN2 缺乏 LIM 结构域。我们的结果初步表明 的形成受 调节。根据体外和体内实验,三种剪接异构体在骨骼肌中具有不同的功能。最后,我们通过与 和 的相互作用鉴定了不同变体发挥不同作用的机制,这反过来又促进了鸡成肌细胞的增殖和分化,从而调节鸡肌发生。总之,本研究揭示了三种 变体在鸡肌发生和肌肉重塑中的不同作用,并通过蛋白-蛋白相互作用阐明了它们的调节机制。