Recent work of a team led by Stoyno Stoynov, working at the Bulgarian Academy of Sciences, suggests that thermodynamic stability of DNA/DNA and RNA/DNA duplexes influences mRNA transcription. The manuscript appears in the March 14 issue of the international, peer-reviewed, open-access online journal PLoS ONE.
“These findings challenge the way we look at DNA,” says Stoynov. "Until now we have pretty much simplified our view of DNA helix as a Lego combination of four different pieces, which encodes genetic information and contain patterns, recognized by DNA binding proteins. However, nucleic acids are real molecules with defined physical characteristics, which can influence their biological functions.”
In this work the authors present a calculation of the thermodynamic stability of DNA/DNA and mRNA/DNA duplexes across the genomes of four species in the genus Saccharomyces. The researchers found that genes of these organisms are more stable than intergenic regions near their 3’-end. In addition, introns (internal non-coding regions in genes) are significantly less stable than exons (coding sequences in genes), suggesting that stable sense duplexes are characteristic of the coding sequences.
Next, the authors showed a relationship between the pattern of thermodynamic stability and the mRNA level of genes. There is a general trend of increased mRNA level with increasing thermodynamic stability of the respective gene. Positive correlation was observed between the mRNA level and the stability of DNA/DNA and mRNA/DNA duplexes of both exons and introns. In contrast, an inverse relationship exists between mRNA levels and stability of the region near 3’-end of genes. mRNA levels increase with decreasing thermodynamic stability of this region. “The observed correlations are impressive, given that several other factors like promoter effectiveness, promoter regulation, and mRNA half-life directly influence mRNA level, as well,” says Stoynov.
The researchers also observed that, in contrast to intergenic regions, genes have more stable sense RNA/DNA duplexes than potential antisense RNA/DNA duplexes. “The difference between stability of sense and antisense mRNA/DNA is a property that can aid gene discovery,” explains Stoynov.
“Thermodynamic stability of nucleic acid duplexes depends primarily on thermodynamic properties of nearest-neighbor nucleotide interactions. Therefore, the stability of DNA/DNA and RNA/DNA duplexes is determined by the distribution of the ten possible DNA/DNA nucleotide duplets (dAA/dTT, dGC/dCG, etc.) and the sixteen possible RNA/DNA duplets (rAA/dTT, rUA/dAT, etc.). Such duplet code does not carry any genetic information but seems to modulate the level of RNA expression. It is amazing that the same nucleotide sequence can simultaneously encode its respective protein and modulate its level of expression.” says Stoynov.
The mechanism of how DNA/DNA and mRNA/DNA duplex stability influences mRNA level remains unclear. The authors propose two models, but further work is needed to understand how thermodynamic stability modulates mRNA level.
The study was funded by Alexander von Humboldt Foundation Return Fellowship and NATO Grant EAP.RIG.981642.
The work was conducted by current and former scientists from the Institute of Molecular Biology at Bulgarian Academy of Sciences. Assen Roguev, Dragomir Krastev, and Anna Ivanova are currently working at the University of California, San Francisco, Max Planck Institute of Molecular Cell Biology and Genetics in Dresden and Carl Gustav Carus Medical School, Dresden University of Technology, respectively. Three of the co-authors (Rayna Kraeva Dragomir Krastev and Anna Ivanova) were diploma students while working on this study. “There is no adequate financial support for PhD students and postdoctoral fellows in Bulgarian scientific institutions. Therefore, I am working predominantly with well prepared and highly motivated diploma students,” says Stoynov.
The Institute of Molecular Biology at the Bulgarian Academy of Sciences was founded in 1960 and is the leading research and training institution in Bulgaria in the field of molecular biology and biochemistry.
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences