![]() ![]() More recently, the roles of the E peptide in regulating IGF1 function have come under scrutiny, especially with respect to myoblast proliferation and muscle repair. It has been proposed that class 1 transcripts might be associated with an autocrine/paracrine role and have a stronger ability to interact with insulin-like growth factor-binding proteins ( 13), whereas class 2 transcripts represent the endocrine form and are thought to be more growth hormone (GH)-dependent ( 14, 15). Class 1 transcripts are widely expressed in all tissues with relatively high levels, whereas class 2 transcripts are expressed in only a few tissues with low levels, except in the liver ( 8, 11). Finally, this alternative splicing leads to different signal peptides and E peptides of the IGF1 protein domains.ĭifferent splice variants of the IGF1 gene have different expression patterns and various functions ( 11, 12). Moreover, the splice variant containing both exons 5 and 6 is referred to as IGF1 Ec (also known as mechano growth factor). Meanwhile, according to the difference in the carboxy-terminus, the splice variants containing exon 5 or exon 6 are generally referred to as IGF1 Eb or IGF1 Ea, respectively. Briefly, according to differences in the leader, the splice variants starting from exon 1 or exon 2 are referred to as class 1 or class 2 IGF1, respectively. The IGF1 proteins are named according to differences in the leader and carboxy-terminus ( 8). IGF1 is conserved across species and contains six exons that can be alternatively spliced into multiple transcripts, encoding different pre-pro-IGF1 proteins ( 8, 9, 10). The important role of IGF1 in growth and development makes it a promising candidate gene for the marker-assisted selection of growth traits ( 5).Īlternative splicing, occurring in over 95% of human genes and over 63% of mouse genes, plays key roles in the regulation of gene expression and diversification of both the transcriptome and encoded proteome ( 6, 7). It is widely recognized that IGF1 is essential for the regulation of normal growth ( 1), development ( 2), immunity ( 3), and metabolism ( 4) in vertebrate species. Insulin-like growth factor 1 (IGF1), also known as somatomedin C, has remarkable diversity in terms of biological effects. In summary, the four ovine IGF1 splice variants have different structures and expression patterns and might have different biological functions. Among the four splice variants, class 1-Ea had a more evident effect on cell proliferation and apoptosis. In contrast, silencing IGF1 Ea or IGF1 Eb with siRNA significantly inhibited proliferation and promoted apoptosis ( P < 0.05). Overexpression of the four splice variants significantly increased fibroblast proliferation and inhibited apoptosis ( P < 0.05). Overall, levels of the four IGF1 splice variants at the fetal and lamb stages were higher than those at the adult stage. In most tissues and stages, the expression of class 1-Ea was highest, and the expression of other splice variants was low. Tissue expression analysis indicated that the four splice variants were broadly expressed in all tested tissues and were most abundantly expressed in the liver. Bioinformatics analysis showed that the four splice variants shared the same mature peptide (70 amino acids) and possessed distinct signal peptides and E peptides. 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. However, the exact alternative splicing patterns of IGF1 and the sequence information of different splice variants in sheep are still unclear. In many species, the IGF1 gene can be alternatively spliced into multiple transcripts, encoding different pre-pro-IGF1 proteins. Insulin-like growth factor 1 (IGF1), also known as somatomedin C, is essential for the regulation of animal growth and development.
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