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.

Selection on codon bias in yeast: a transcriptional hypothesis

“…It has also been suggested that the thermodynamic stability of DNA/DNA and mRNA/DNA duplexes affects mRNA transcription (24). Here, we analyze the genome-wide data for the calculated thermodynamic stability of DNA/DNA and RNA/DNA duplexes in yeast obtained from published sources (24).…”

“…Intron sequences were downloaded from the Ares lab Intron Database (version 3.0) (http://compbio.soe.ucsc.edu/yeast_introns.html). From literature sources, we obtained data sets for the transcriptome (19–22), protein abundance (23), the average values of ΔG for mRNA/DNA and DNA/DNA duplex stabilities of CDS (window size 9 bp) (24), nucleosome occupancy (25), protein and mRNA high-confidence cellular levels of 408 genes (26) and parallel analysis of RNA structure (PARS) scores (27). …”

Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium

“…While these ideas are speculative, studies on RNA/DNA hybrid stability support these ideas. In particular, poly-rU/poly-dA hybrids (akin to those occurring just upstream of the TSS) are the least stable, and poly-rA/poly-dT hybrids (akin to the downstream arrangement) are the most stable of all RNA/DNA hybrid tracts consisting of only A or T (or U) (Sugimoto et al 1995;Kraeva et al 2007).…”

The thermodynamic patterns of eukaryotic genes suggest a mechanism for intron–exon recognition

“…It has been shown [8][9][10] that the 5 0 -and 3 0 -untranslated regions (UTRs), introns and exons have characteristic guanine/cytosine (GC) content, which could affect RNA transcription and processing. Nucleotide composition could influence protein recruitment 9 , RNA secondary structure 10 , transcription rate 11,12 , DNA melting 13 or RNA/DNA and DNA/DNA duplex stability 14 . The free energy (DG) necessary to unwind polynucleotide duplexes with defined length can be calculated from the measured values of entropy (DS) and enthalpy (DH) for the 10 possible nearest-neighbour DNA/ DNA [15][16][17][18][19][20] interactions, and the 16 possible RNA/DNA 21,22 interactions.…”

“…The free energy (DG) necessary to unwind polynucleotide duplexes with defined length can be calculated from the measured values of entropy (DS) and enthalpy (DH) for the 10 possible nearest-neighbour DNA/ DNA [15][16][17][18][19][20] interactions, and the 16 possible RNA/DNA 21,22 interactions. We have previously shown that exons possess more stable RNA/DNA duplexes than introns in Saccharomyces cerevisiae 14 . However, our original approach did not allow for direct comparisons between the stability of RNA/DNA and DNA/ DNA duplexes because the DS and DH parameters used for DNA/ DNA duplexes 19 lead to overestimation of its DG in comparison with DG of RNA/DNA duplexes.…”