In silico analysis of miRNA-mediated gene regulation in OCA and OA genes.

Abstract

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.

• Authors: Balu Kamaraj, Chandrasekhar Gopalakrishnan, Rituraj Purohit
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 70 Issue 3 Pg. 1923-32 (Dec 2014) ISSN: 1559-0283 [Electronic] United States
• PMID: 25060099 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• Antigens, Neoplasm
• Eye Proteins
• GPR143 protein, human
• Membrane Glycoproteins
• Membrane Transport Proteins
• MicroRNAs
• RNA, Messenger
• SLC45A2 protein, human

Topics

• 3' Untranslated Regions
• Albinism, Ocular (genetics, pathology)
• Albinism, Oculocutaneous (genetics, pathology)
• Algorithms
• Alleles
• Antigens, Neoplasm (genetics)
• Binding Sites
• Databases, Genetic
• Expressed Sequence Tags
• Eye Proteins (genetics)
• Gene Expression Regulation
• Gene Regulatory Networks
• Humans
• Membrane Glycoproteins (genetics)
• Membrane Transport Proteins (genetics)
• MicroRNAs (metabolism)
• Polymorphism, Single Nucleotide
• RNA, Messenger (chemistry, metabolism)