Minimum Free Energy Based Evaluation of mRNAs Secondary Structures Constructed by 18 Clinically Significant Exonic Single Nucleotide Polymorphisms (SNPs) and Haplotypes of 5 Missense SNPs of RB1 Gene

Sarder Nasir Uddin,Sk Amir Hossain,Khandker Khaldun Islam,Apurba Majumder,Palash Kumar Sarker

doi:10.3844/ajbbsp.2015.191.199

Abstract

Clinically significant 18 Single Nucleotide Polymorphisms (SNPs) from exon regions of Retinoblastoma gene (RB1) were analyzed to find out the structural variations in mRNAs. Online bioinformatic tools i.e., Vienna RNA, RNAfold were used for secondary structure analysis of mRNAs. Predicted minimum Free Energy Change (MFE) was calculated for mRNAs structures. It has been observed that the average of predicted MFE value from 13 nonsense mutations was higher (0.76 kcal/mol) in comparison to 5 missense mutations. Presumably, 13 nonsense mutations are responsible for Nonsense Mediated mRNA Decay (NMD), therefore, excluded from haplotype analysis. From the statistical analysis all the thermodynamic data obtained from four SNP haplotypes are significant (p≤0.05), followed by three-SNP haplotype data except Ensemble diversity (p≤0.10). Interestingly, MEF of Centroid Secondary Structure is highly significant (p≤0.01) in all the cases (Two-SNP haplotypes, Three-SNP haplotypes and Four-SNP haplotypes).

Highlights

Role of RNAs in regulation of gene networks is well characterized and the execution of the regulatory activities of the mRNA involves a wide range interaction with proteins, limiting RNA confirmation in vivo (Gregory, 2015; Shabalina et al, 2014; 2013; Laederach, 2007)
We were focused on the Single Nucleotide Polymorphisms (SNPs) database found in National Center for Biotechnology Information (NCBI; www.ncbi.nlm.nih.gov/snp/?term=Retinoblastoma) which is a part of the United States National Library of Medicine (NLM)
In the dbSNP of NCBI many SNPs has been reported for RB1 gene region, we identified 18 exonic SNPs to be included within our range of study as they are clinically significant in Locus Specific Database (LSDB) submission with appropriate research findings

Summary

Introduction

Role of RNAs in regulation of gene networks is well characterized and the execution of the regulatory activities of the mRNA involves a wide range interaction with proteins, limiting RNA confirmation in vivo (Gregory, 2015; Shabalina et al, 2014; 2013; Laederach, 2007). Thereby, DNA variants based structural changes of mRNA secondary structure likely affects the protein translation efficiency (Mita and Kuroiwa, 1989; Schmittgen et al, 1994; Shalev et al, 2002), while majority of mutations are transferred to the transcriptome (Morton, 2008). Catecho-O-Mrthyltransferase (COMT) is a key regulator of pain, cognitive function and affective mood, modulate the protein expression by altering the mRNA secondary structure in presence of Single Nucleotide Polymorphism (SNP) (Nackley et al, 2006). Secondary structural analysis is focused on the functional motifs of mRNAs to determine the thermodynamic properties, i.e., Minimum Free Energy (MFE). The secondary structures of mRNAs could be analyzed based on the MFE and the ensemble optimal structures provided by different secondary structure prediction bioinformatic tools (Mathews et al, 1999; Johnson et al, 2011)

Methods

Results

Discussion

Conclusion