PDF(Pubmed)
Abstract：
Haem oxygenase-1 (HO-1) is a ubiquitously expressed gene involved in cellular homoeostasis, and its imbalance in expression results in various disorders. To alleviate such disorders, HO-1 gene expression needs to be modulated. Codon usage bias results from evolutionary forces acting on any nucleotide sequence and determines the gene expression. Like codon usage bias, codon pair bias also exists, playing a role in gene expression. In the present study, HO-1 gene was recoded by manipulating codon and codon pair bias, and four such constructs were made through codon/codon pair deoptimization and codon/codon pair optimization to reduce and enhance the HO-1 gene expression. Codon usage analysis was done for these constructs for four tissues brain, heart, pancreas and liver. Based on codon usage in different tissues, gene expression of these tissues was determined in terms of the codon adaptation index. Based on the codon adaptation index, minimum free energy, and translation efficiency, constructs were evaluated for enhanced or decreased HO-1 expression. The analysis revealed that for enhancing gene expression, codon pair optimization, while for reducing gene expression, codon deoptimization is efficacious. The recoded constructs developed in the study could be used in gene therapy regimens to cure HO-1 over or underexpression-associated disorders.
摘要：
血红素加氧酶-1（HO-1）是一个广泛表达的基因，涉及细胞的同质性。其表达失衡导致各种疾病。为了缓解这种疾病，需要调节HO-1基因表达。密码子使用偏差是由作用于任何核苷酸序列的进化力引起的，并决定了基因表达。像密码子使用偏差一样，密码子对偏倚也存在，在基因表达中发挥作用。在本研究中,通过操纵密码子和密码子对偏倚对HO-1基因进行编码,通过密码子/密码子对解优化和密码子/密码子对优化制备四个这样的构建体以减少和增强HO-1基因表达。对这些构建体的四种脑组织进行了密码子使用分析，心,胰腺和肝脏。根据不同组织中的密码子使用情况,根据密码子适应指数确定这些组织的基因表达。根据密码子适应指数,最低自由能,和翻译效率，评估构建体的HO-1表达增强或降低。分析显示，为了增强基因表达，密码子对优化，而为了减少基因表达，密码子去优化是有效的。研究中开发的重新编码的构建体可用于基因治疗方案，以治愈HO-1过度或表达不足相关的疾病。
