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Stability of mRNA/DNA and DNA/DNA duplexes affects mRNA transcription.

Kraeva RI, Krastev DB, Roguev A, Ivanova A, Nedelcheva-Veleva MN, Stoynov SS - PLoS ONE (2007)

Bottom Line: The results show that coding regions are more thermodynamically stable than introns, 3'-untranslated regions and intergenic sequences.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

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.

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Thermodynamic stability (ΔG) of the nearest-neighbor interactions in RNA/DNA duplexes (10 mM monovalent cation), containing complementary DNA strands (in blue). Watson strand (top) and Crick strand (bottom) shown in black.
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pone-0000290-g004: Thermodynamic stability (ΔG) of the nearest-neighbor interactions in RNA/DNA duplexes (10 mM monovalent cation), containing complementary DNA strands (in blue). Watson strand (top) and Crick strand (bottom) shown in black.

Mentions: To explain the observed differences in the stability of sense and potential antisense RNA/DNA duplexes in coding sequences and introns, we calculated the frequency of their nearest neighbor interactions. RNA/DNA nearest neighbor interactions form pairs, containing complementary DNA duplets (Figure 4). Differences in ΔG values of for interactions within these pairs are responsible for the difference in stability of sense/antisense duplexes. We found that genes' sense mRNA/DNA duplexes contain more rAA/dTT, rAC/dTG, rAG/dTC, rGG/dCC, rGA/dCT, rCA/dGT interactions than their corresponding partners rUU/dAA, rGU/dCA, rCU/dGA, rCC/dGG, rUC/dAG, rUG/dAC found more frequently in the potential antisense RNA/DNA duplexes (Table S7). The higher stability of the first five sense interactions (rAA/dTT, rAC/dTG, rAG/dTC, rGG/dCC, rUC/dAG) compared to the corresponding antisense partners (rUU/dAA, rGU/dCA, rCU/dGA, rCC/dGG, rGA/dCT) leads to a more stable sense RNA/DNA duplex. rUG/dAC is more stable and well-represented in antisense duplexes than rCA/dGT and hence it contributes to the stability of the antisense duplex. Finally, rAU/dTA and rUA/dAT, as well as rGC/dCG and rCG/dGC, are symmetric and therefore equally distributed in both sense and antisense duplexes and contribute equally to their stability. Yet, the impact of the first five duplex pairs on the stability of the sense duplex is much stronger and consequently sense duplexes are more stable than antisense duplexes. In introns and IGRs, however, the above frequencies are different (Tables S8 and S9). For example, in contrast to coding sequences, the more stable rAA/dTT pair is under-represented in introns compared to its corresponding but less stable rUU/dAA pair. These two pairs occur with nearly equal frequency in IGRs. This suggests that the different distribution of certain nearest neighbor interactions contributes to the higher stability of coding sequences and lower stability of introns and IGRs.


Stability of mRNA/DNA and DNA/DNA duplexes affects mRNA transcription.

Kraeva RI, Krastev DB, Roguev A, Ivanova A, Nedelcheva-Veleva MN, Stoynov SS - PLoS ONE (2007)

Thermodynamic stability (ΔG) of the nearest-neighbor interactions in RNA/DNA duplexes (10 mM monovalent cation), containing complementary DNA strands (in blue). Watson strand (top) and Crick strand (bottom) shown in black.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1808433&req=5

pone-0000290-g004: Thermodynamic stability (ΔG) of the nearest-neighbor interactions in RNA/DNA duplexes (10 mM monovalent cation), containing complementary DNA strands (in blue). Watson strand (top) and Crick strand (bottom) shown in black.
Mentions: To explain the observed differences in the stability of sense and potential antisense RNA/DNA duplexes in coding sequences and introns, we calculated the frequency of their nearest neighbor interactions. RNA/DNA nearest neighbor interactions form pairs, containing complementary DNA duplets (Figure 4). Differences in ΔG values of for interactions within these pairs are responsible for the difference in stability of sense/antisense duplexes. We found that genes' sense mRNA/DNA duplexes contain more rAA/dTT, rAC/dTG, rAG/dTC, rGG/dCC, rGA/dCT, rCA/dGT interactions than their corresponding partners rUU/dAA, rGU/dCA, rCU/dGA, rCC/dGG, rUC/dAG, rUG/dAC found more frequently in the potential antisense RNA/DNA duplexes (Table S7). The higher stability of the first five sense interactions (rAA/dTT, rAC/dTG, rAG/dTC, rGG/dCC, rUC/dAG) compared to the corresponding antisense partners (rUU/dAA, rGU/dCA, rCU/dGA, rCC/dGG, rGA/dCT) leads to a more stable sense RNA/DNA duplex. rUG/dAC is more stable and well-represented in antisense duplexes than rCA/dGT and hence it contributes to the stability of the antisense duplex. Finally, rAU/dTA and rUA/dAT, as well as rGC/dCG and rCG/dGC, are symmetric and therefore equally distributed in both sense and antisense duplexes and contribute equally to their stability. Yet, the impact of the first five duplex pairs on the stability of the sense duplex is much stronger and consequently sense duplexes are more stable than antisense duplexes. In introns and IGRs, however, the above frequencies are different (Tables S8 and S9). For example, in contrast to coding sequences, the more stable rAA/dTT pair is under-represented in introns compared to its corresponding but less stable rUU/dAA pair. These two pairs occur with nearly equal frequency in IGRs. This suggests that the different distribution of certain nearest neighbor interactions contributes to the higher stability of coding sequences and lower stability of introns and IGRs.

Bottom Line: The results show that coding regions are more thermodynamically stable than introns, 3'-untranslated regions and intergenic sequences.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

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.

Show MeSH
Related in: MedlinePlus