Song Xu-Ting, Zhang Jia-Nan, Zhao Duo-Wei, Zhai Yu-Fei, Lu Qi, Qi Mei-Yu, Lu Ming-Hai, Deng Shou-Long, Han Hong-Bing, Yang Xiu-Qin, Yao Yu-Chang
Key Laboratory of Animal Genetics, Breeding and Reproduction, Education Department of Heilongjiang Province, College of Animal Science and Technology, Northeast Agricultural University, Harbin, China.
Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin, China.
Endocr Connect. 2021 Aug 24;10(9):980-994. doi: 10.1530/EC-21-0181.
Insulin-like growth factor 1 (IGF1), also known as somatomedin C, is essential for the regulation of animal growth and development. In many species, the IGF1 gene can be alternatively spliced into multiple transcripts, encoding different pre-pro-IGF1 proteins. However, the exact alternative splicing patterns of IGF1 and the sequence information of different splice variants in sheep are still unclear. In this study, four splice variants (class 1-Ea, class 1-Eb, class 2-Ea, and class 2-Eb) were obtained, but no IGF1 Ec, similar to that found in other species, was discovered. Bioinformatics analysis showed that the four splice variants shared the same mature peptide (70 amino acids) and possessed distinct signal peptides and E peptides. Tissue expression analysis indicated that the four splice variants were broadly expressed in all tested tissues and were most abundantly expressed in the liver. In most tissues and stages, the expression of class 1-Ea was highest, and the expression of other splice variants was low. Overall, levels of the four IGF1 splice variants at the fetal and lamb stages were higher than those at the adult stage. Overexpression of the four splice variants significantly increased fibroblast proliferation and inhibited apoptosis (P < 0.05). In contrast, silencing IGF1 Ea or IGF1 Eb with siRNA significantly inhibited proliferation and promoted apoptosis (P < 0.05). Among the four splice variants, class 1-Ea had a more evident effect on cell proliferation and apoptosis. In summary, the four ovine IGF1 splice variants have different structures and expression patterns and might have different biological functions.
胰岛素样生长因子1（IGF1），也被称为生长调节素C，对动物生长发育的调节至关重要。在许多物种中，IGF1基因可以选择性剪接成多个转录本，编码不同的前胰岛素原生长因子1蛋白。然而，绵羊中IGF1的确切选择性剪接模式以及不同剪接变体的序列信息仍不清楚。在本研究中，获得了四个剪接变体（1-Ea类、1-Eb类、2-Ea类和2-Eb类），但未发现与其他物种中存在的IGF1 Ec类似的变体。生物信息学分析表明，这四个剪接变体共享相同的成熟肽（70个氨基酸），并具有不同的信号肽和E肽。组织表达分析表明，这四个剪接变体在所有测试组织中广泛表达，在肝脏中表达最为丰富。在大多数组织和阶段，1-Ea类的表达最高，其他剪接变体的表达较低。总体而言，四个IGF1剪接变体在胎儿和羔羊阶段的水平高于成年阶段。这四个剪接变体的过表达显著增加了成纤维细胞增殖并抑制了细胞凋亡（P<0.05）。相反，用小干扰RNA沉默IGF1 Ea或IGF1 Eb显著抑制了增殖并促进了细胞凋亡（P<0.05）。在这四个剪接变体中，1-Ea类对细胞增殖和凋亡的影响更为明显。总之，四个绵羊IGF1剪接变体具有不同的结构和表达模式，可能具有不同的生物学功能。
