In Silico Analysis of miRNA-Mediated Gene Regulation in OCA and OA Genes
In Silico Analysis of miRNA-Mediated Gene Regulation in OCA and OA Genes
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DOI：
10.1007/s12013-014-0152-9
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发表时间：
2014-12-01
影响因子：
2.6
通讯作者：
Purohit, Rituraj
中科院分区：
文献类型：
--
作者：
Kamaraj, Balu;Gopalakrishnan, Chandrasekhar;Purohit, Rituraj
白化病是一种常染色体隐性遗传疾病，由于低分泌的黑色素。眼皮肤白化病（OCA）和眼白化病（OA）基因负责黑色素的产生，也是miRNA的潜在靶点。miRNA的作用是通过与mRNA的3'UTR结合从而调节基因表达，从而部分或完全抑制蛋白质合成。在该分析中，我们预测了发生在转录物的3'UTR中的遗传变异，这可能是黑色素产生低从而导致白化病的原因。3'UTR上的单核苷酸多态性（single nucleotide polymorphism，SNPs）使miRNA产生更多的新的结合位点，与mRNA结合，从而部分或完全抑制mRNA的翻译过程。OCA和OA基因mRNA中的SNP可以为miRNA产生新的结合位点，从而控制基因表达并导致色素减退。我们已经开发了一个计算程序来确定OCA（TYR，OCA 2，TYRP 1和SLC 45 A2）和OA（GPR 143）基因mRNA的3'UTR区域的SNPs，这将是一个潜在的白化病的原因。我们在5个基因中发现了37个SNPs，预计它们会在mRNA上产生87个新的结合位点，这可能会导致翻译过程的废除。表达分析证实这些基因在皮肤和眼睛区域高度表达。富集分析充分支持这些基因主要参与眼睛色素沉着和黑色素生物合成过程。网络分析还显示了基因如何在复杂网络中相互作用和表达。这一发现为湿实验室研究OCA和OA基因的表达模式以及突变后mRNA和miRNA的结合现象提供了线索，这是在基因组水平上抑制翻译过程的原因。
Albinism is an autosomal recessive genetic disorder due to low secretion of melanin. The oculocutaneous albinism (OCA) and ocular albinism (OA) genes are responsible for melanin production and also act as a potential targets for miRNAs. The role of miRNA is to inhibit the protein synthesis partially or completely by binding with the 3'UTR of the mRNA thus regulating gene expression. In this analysis, we predicted the genetic variation that occurred in 3'UTR of the transcript which can be a reason for low melanin production thus causing albinism. The single nucleotide polymorphisms (SNPs) in 3'UTR cause more new binding sites for miRNA which binds with mRNA which leads to inhibit the translation process either partially or completely. The SNPs in the mRNA of OCA and OA genes can create new binding sites for miRNA which may control the gene expression and lead to hypopigmentation. We have developed a computational procedure to determine the SNPs in the 3'UTR region of mRNA of OCA (TYR, OCA2, TYRP1 and SLC45A2) and OA (GPR143) genes which will be a potential cause for albinism. We identified 37 SNPs in five genes that are predicted to create 87 new binding sites on mRNA, which may lead to abrogation of the translation process. Expression analysis confirms that these genes are highly expressed in skin and eye regions. It is well supported by enrichment analysis that these genes are mainly involved in eye pigmentation and melanin biosynthesis process. The network analysis also shows how the genes are interacting and expressing in a complex network. This insight provides clue to wet-lab researches to understand the expression pattern of OCA and OA genes and binding phenomenon of mRNA and miRNA upon mutation, which is responsible for inhibition of translation process at genomic levels.