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Modeling RNA polymerase competition: the effect of σ-subunit knockout and heat shock on gene transcription level.

Lyubetsky VA, Zverkov OA, Rubanov LI, Seliverstov AV - Biol. Direct (2011)

Bottom Line: Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics.The source code written in C++ is available under the GNU General Public License from the laboratory website.The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Information Transmission Problems of the Russian Academy of Sciences (Kharkevich Institute), 19 Bolshoy Karetny per,, Moscow, Russia. lyubetsk@iitp.ru

ABSTRACT

Background: Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination.

Results: A mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at http://lab6.iitp.ru/en/rivals.

Conclusions: The developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation.

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Multiple alignment of putative transcription terminator T1 of genes psbT and psbN in chloroplasts of eurosids II. Complete intergenic region is shown (in Arabidopsis its position is 74184-74248). Arrows and colors mark complementary shoulders in the palindrome. Asterisks mark conserved positions, dashes denote gaps.
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Figure 3: Multiple alignment of putative transcription terminator T1 of genes psbT and psbN in chloroplasts of eurosids II. Complete intergenic region is shown (in Arabidopsis its position is 74184-74248). Arrows and colors mark complementary shoulders in the palindrome. Asterisks mark conserved positions, dashes denote gaps.

Mentions: For Locus 1 and gene ycf1 transcription level ratios were experimentally identified for its three promoters [8] and they are well reproduced in the model. For Locus 2 the predictions are in good agreement with the experimental data on transcription level changes during heat shock of isolated chloroplasts not affected by nuclear encoded heat shock proteins. For Locus 3 terminator T1 was predicted to exist between genes psbT and psbN adjoining the 3'-end of psbN in chloroplasts of Arabidopsis thaliana. It was validated on the multiple alignment of corresponding region to occur widely in plastids of plants and algae, see also [30]. In chloroplasts of eurosids II it is a palindrome structure of 44 nt length with the consensus TTGAMGTAATCAGCCTCCMAATATTKGGAGGCTGATTACKTCAA (Figure 3).


Modeling RNA polymerase competition: the effect of σ-subunit knockout and heat shock on gene transcription level.

Lyubetsky VA, Zverkov OA, Rubanov LI, Seliverstov AV - Biol. Direct (2011)

Multiple alignment of putative transcription terminator T1 of genes psbT and psbN in chloroplasts of eurosids II. Complete intergenic region is shown (in Arabidopsis its position is 74184-74248). Arrows and colors mark complementary shoulders in the palindrome. Asterisks mark conserved positions, dashes denote gaps.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3038987&req=5

Figure 3: Multiple alignment of putative transcription terminator T1 of genes psbT and psbN in chloroplasts of eurosids II. Complete intergenic region is shown (in Arabidopsis its position is 74184-74248). Arrows and colors mark complementary shoulders in the palindrome. Asterisks mark conserved positions, dashes denote gaps.
Mentions: For Locus 1 and gene ycf1 transcription level ratios were experimentally identified for its three promoters [8] and they are well reproduced in the model. For Locus 2 the predictions are in good agreement with the experimental data on transcription level changes during heat shock of isolated chloroplasts not affected by nuclear encoded heat shock proteins. For Locus 3 terminator T1 was predicted to exist between genes psbT and psbN adjoining the 3'-end of psbN in chloroplasts of Arabidopsis thaliana. It was validated on the multiple alignment of corresponding region to occur widely in plastids of plants and algae, see also [30]. In chloroplasts of eurosids II it is a palindrome structure of 44 nt length with the consensus TTGAMGTAATCAGCCTCCMAATATTKGGAGGCTGATTACKTCAA (Figure 3).

Bottom Line: Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics.The source code written in C++ is available under the GNU General Public License from the laboratory website.The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Information Transmission Problems of the Russian Academy of Sciences (Kharkevich Institute), 19 Bolshoy Karetny per,, Moscow, Russia. lyubetsk@iitp.ru

ABSTRACT

Background: Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination.

Results: A mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at http://lab6.iitp.ru/en/rivals.

Conclusions: The developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation.

Show MeSH
Related in: MedlinePlus