Stability of mRNA/DNA and DNA/DNA Duplexes Affects mRNA Transcription

Rayna I Kraeva,Stoyno S Stoynov,Dragomir B Krastev,Marina N Nedelcheva-Veleva,Anna Ivanova,Assen Roguev,Stefan Maas

doi:10.1371/journal.pone.0000290

Rayna I Kraeva, Stoyno S Stoynov + Show 5 more

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https://doi.org/10.1371/journal.pone.0000290

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Abstract

Nucleic acids, due to their structural and chemical properties, can form double-stranded secondary structures that assist the transfer of genetic information and can modulate gene expression. However, the nucleotide sequence alone is insufficient in explaining phenomena like intron-exon recognition during RNA processing. This raises the question whether nucleic acids are endowed with other attributes that can contribute to their biological functions. In this work, we present a calculation of thermodynamic stability of DNA/DNA and mRNA/DNA duplexes across the genomes of four species in the genus Saccharomyces by nearest-neighbor method. The results show that coding regions are more thermodynamically stable than introns, 3′-untranslated regions and intergenic sequences. Furthermore, open reading frames have more stable sense mRNA/DNA duplexes than the potential antisense duplexes, a property that can aid gene discovery. The lower stability of the DNA/DNA and mRNA/DNA duplexes of 3′-untranslated regions and the higher stability of genes correlates with increased mRNA level. These results suggest that the thermodynamic stability of DNA/DNA and mRNA/DNA duplexes affects mRNA transcription.

Highlights

In living systems DNA provides information for the synthesis of RNAs and proteins
We found that intergenic regions (IGRs) have lower mean values of DG average and DG minimum (DG avg = 92.84 kcal/mol and DG min = 78.60 kcal/mol) than genes (DG avg = 100.80 kcal/mol and DG min = 84.81 kcal/mol) (Figure 1 and Tables S1, S2 and S3)
In order to distinguish the roles of the observed differences in duplex stability in transcription initiation and transcription termination, we grouped the intergenic regions into three groups based on the direction of transcription of their neighboring open reading frames (ORFs): (i) IGRs between ORF starts, (ii) IGRs between ORF ends and (iii) IGRs between two ORFs transcribed in the same direction (Table S2)

Summary

Introduction

In living systems DNA provides information for the synthesis of RNAs and proteins. The secondary structure of nucleic acids through its defined physico-chemical characteristics such as the thermodynamic stability of the pairing between the two strands can influence its biological function. The thermodynamic stability of a polynucleotide duplex is defined as the free energy (DG) required to unwind it and can be calculated from the entropy (DS) and the enthalpy (DH) of the pairing between the adjacent bases using a nearest-neighbor method [1]. Published calorimetric measurement of DS and DH of all possible nearest-neighbor interactions of DNA/DNA [2] and RNA/DNA [3] duplexes allows for calculation of thermodynamic stability of polynucleotide duplexes with a defined sequence [4,5,6]. MRNA/DNA duplexes appear to be more stable than the corresponding anti-sense duplexes, allowing prediction of open reading frames. Based on these observations the role of thermodynamic stability on transcription is discussed

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