Modeling RNA polymerase interaction in mitochondria of chordates

Abstract

BackgroundIn previous work, we introduced a concept, a mathematical model and its computer realization that describe the interaction between bacterial and phage type RNA polymerases, protein factors, DNA and RNA secondary structures during transcription, including transcription initiation and termination. The model accurately reproduces changes of gene transcription level observed in polymerase sigma-subunit knockout and heat shock experiments in plant plastids. The corresponding computer program and a user guide are available at http://lab6.iitp.ru/en/rivals. Here we apply the model to the analysis of transcription and (partially) translation processes in the mitochondria of frog, rat and human. Notably, mitochondria possess only phage-type polymerases. We consider the entire mitochondrial genome so that our model allows RNA polymerases to complete more than one circle on the DNA strand.ResultsOur model of RNA polymerase interaction during transcription initiation and elongation accurately reproduces experimental data obtained for plastids. Moreover, it also reproduces evidence on bulk RNA concentrations and RNA half-lives in the mitochondria of frog, human with or without the MELAS mutation, and rat with normal (euthyroid) or hyposecretion of thyroid hormone (hypothyroid). The transcription characteristics predicted by the model include: (i) the fraction of polymerases terminating at a protein-dependent terminator in both directions (the terminator polarization), (ii) the binding intensities of the regulatory protein factor (mTERF) with the termination site and, (iii) the transcription initiation intensities (initiation frequencies) of all promoters in all five conditions (frog, healthy human, human with MELAS syndrome, healthy rat, and hypothyroid rat with aberrant mtDNA methylation). Using the model, absolute levels of all gene transcription can be inferred from an arbitrary array of the three transcription characteristics, whereas, for selected genes only relative RNA concentrations have been experimentally determined. Conversely, these characteristics and absolute transcription levels can be obtained using relative RNA concentrations and RNA half-lives known from various experimental studies. In this case, the “inverse problem” is solved with multi-objective optimization.ConclusionsIn this study, we demonstrate that our model accurately reproduces all relevant experimental data available for plant plastids, as well as the mitochondria of chordates. Using experimental data, the model is applied to estimate binding intensities of phage-type RNA polymerases to their promoters as well as predicting terminator characteristics, including polarization. In addition, one can predict characteristics of phage-type RNA polymerases and the transcription process that are difficult to measure directly, e.g., the association between the promoter’s nucleotide composition and the intensity of polymerase binding. To illustrate the application of our model in functional predictions, we propose a possible mechanism for MELAS sy...

A Database of Plastid Protein Families from Red Algae and Apicomplexa and Expression Regulation of themoeBGene

“…An important role of such competition in expression of closely located antidirected genes is substantiated in modelling and various experiments on gene expression. Such evidence includes data on bacterial type RNA polymerases σ -subunit knockout in plastids of Arabidopsis thaliana and data for mitochondrial RNA polymerases of the phage type [ 38 , 39 ]. Therefore, the moeB promoter is likely to be located in between genes moeB and trnW and requires transcription initiation due to absence of an evident −35 box.…”

“…In Section 3 we essentially exploit the originally proposed model of RNA polymerase competition [ 38 , 39 ]. The model describes the following situation.…”

Transcription Regulation of Plastid Genes Involved in Sulfate Transport in Viridiplantae

“…Relevant promoter sequences and the evolutionary impact of DNA point mutations on polymerase binding affinity are described in [15, 16]; experimental evidence was obtained using the psbA promoter of Sinapis alba [17]. …”

Optimal Growth Temperature and Intergenic Distances in Bacteria, Archaea, and Plastids of Rhodophytic Branch

“…e following condition is considered: X and Y are greater than the predefined thresholds varied in modeling. Our model of interaction between RNA polymerases [18,19] evaluates transcription levels for all genes in a locus of interest. e level is defined as the number of gene transcription events within a fixed time period (3 h in this case).…”