A synonymous mutation in IGF-1 impacts the transcription and translation process of gene expression

Abstract

Insulin-like growth factor 1 (IGF-1) is considered to be a crucial gene in the animal development of bone and body size. In this study, a unique synonymous mutation (c.258 A > G) of the IGF-1 gene was modified with an adenine base editor to observe the growth and developmental situation of mutant mice. Significant expression differences and molecular mechanisms among vectors with different alanine synonymous codons were explored. Although modification of a single synonymous codon rarely interferes with animal phenotypes, we observed that the expression and secretion of IGF-1 were different between 8-week-old homozygous (Ho) and wildtype (WT) mice. In addition, the IGF-1 with optimal codon combinations showed a higher expression content than other codon combination modes at both transcription and translation levels and performed proliferation promotion. The gene stability and translation initiation efficiency also changed significantly. Our findings illustrated that the synonymous mutation altered the IGF-1 gene expression in individual mice and suggested that the synonymous mutation affected the IGF-1 expression and biological function through the transcription and translation processes.

The effects of mutations on gene expression and alternative splicing

“…Missense variants are known to alter the amino acid sequence, and have been shown to impact the interacting DNA-transcription factors, resulting in changed expression of other genes [87]. Low-impact variants including synonymous variants have also been shown to influence gene expression by disrupting transcription and splicing, as well as mRNA stability [88–91].…”

“…Missense variants are known to alter the amino acid sequence, and have been shown to impact the interacting DNA-transcription factors, resulting in changed expression of other genes [87]. Low-impact variants including synonymous variants have also been shown to influence gene expression by disrupting transcription and splicing, as well as mRNA stability [88][89][90][91]. High-impact variants consisted of two downregulated splice acceptor variants, two upregulated start-lost variants, and the upregulation of most stop-gained variants (electronic supplementary material, figure S2).…”

Expression Analysis of a Novel Oxidoreductase Glutaredoxin 2 in Black Tiger Shrimp, Penaeus monodon

“…Since this mutation did not involve alteration of the encoded protein, the specific mode of its effect requires further investigation. Despite the long-standing neutral function of synonymous mutations, studies in recent years have demonstrated that synonymous mutations affect the efficiency and stability of transcription and translation of genes [ 40 , 41 , 42 ]. PmGrx2 -E3398 could be developed as a molecular marker for breeding shrimp tolerant to stress.…”

The effects of mutations on gene expression and alternative splicing: a case study of EMS-induced heritable mutations in the microcrustaceanDaphnia

“…Missense variants are known to alter the amino acid sequence, and have been shown to impact the interacting DNA-transcription factors, resulting in changed expression of other genes (Ding et al 2015). Low-impact variants including synonymous variants have also been shown to influence gene expression by disrupting transcription and splicing, as well as mRNA stability (Pagani et al 2005, Presnyak et al 2015, Stergachis et al 2013, Wang et al 2021.…”