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

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.

Figure 1. Thermodynamic stability of DNA/DNA (green), sense and antisense RNA/DNA duplexes in a region of chromosome 12 in S. cerevisiae (plots of all sixteen chromosomes are available at http://obzor.bio21.bas.bg/stoyno/).

ΔG of RNA/DNA duplexes (blue), containing RNA identical to Watson coding strand represents the sense strand for Watson's ORFs and antisense strand for Crick's ORFs. ΔG of RNA/DNA duplexes (red), containing RNA identical to Crick coding strand represents the sense strand for Crick's ORFs and antisense strand for Watson's ORFs.

Figure 2. (A) Percentage of ORFs with ΔG values of DNA/DNA and sense mRNA/DNA duplexes higher than ΔG avg and ΔG min of the corresponding 3′-IGRs.

(B) Percentage of ORFs with more stable sense than antisense RNA/DNA duplexes as annotated in SGD.

Figure 3

Scatter plot, showing the relationship of mRNA level (copies per cell) and Δ G (kcal/mol) of EPR mRNA/DNA duplexes and Δ G avg of exon mRNA/DNA duplexes. (A) Relationship between mRNA level and Δ G avg of all coding sequences in intron containing ORFs. (B) Relationship between mRNA level and Δ G avg of coding sequences in intron containing ORFs longer than 2000 bp. (C) Relationship between mRNA level and Δ G for all available EPRs. (D) Relationship between mRNA level and ΔG of EPRs for genes shorter than 250 bp.

Figure 4

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.