Nobukazu Ohki1, Masatoshi Hagiwara. 1. Department of Functional Genomics, Medical Research Institute, 1-5-45 Yushima, Tokyo 113-0034, Japan.
Abstract
MOTIVATION: Recently, biologists learnt that the transport and degradation of transcribed mRNA and protein present critically important steps for the regulation of gene expression through extensive studies of RNA interference, none-sense mediated decay and ubiquitination. However, adequate consideration of these factors has not been done in the past in in silico analysis compared with transcriptional regulations. RESULTS: We have developed a bio-system simulator 'Bio-Object' and assessed the contribution of numerous factors including movements, stability and interactions of both mRNAs and proteins in the virtual cell space to the Drosophila circadian rhythm. The oscillations of period (per), timeless (tim) and Drosophila Clock (dClk) mRNAs and proteins predicted by the simulations agreed with the observed data in Drosophila and were lost with the knock-out of either the per or the dClk gene as observed experimentally. Bio-Object predicts that (1) the stability of dClk mRNA, (2) the stability of dCLK and (3) the affinity of the PER-TIM complex are determinants of the circadian duration. AVAILABILITY: The source code is available for download from http://www.tmd.ac.jp/mri/mri-end/bio-object/download/
MOTIVATION: Recently, biologists learnt that the transport and degradation of transcribed mRNA and protein present critically important steps for the regulation of gene expression through extensive studies of RNA interference, none-sense mediated decay and ubiquitination. However, adequate consideration of these factors has not been done in the past in in silico analysis compared with transcriptional regulations. RESULTS: We have developed a bio-system simulator 'Bio-Object' and assessed the contribution of numerous factors including movements, stability and interactions of both mRNAs and proteins in the virtual cell space to the Drosophila circadian rhythm. The oscillations of period (per), timeless (tim) and DrosophilaClock (dClk) mRNAs and proteins predicted by the simulations agreed with the observed data in Drosophila and were lost with the knock-out of either the per or the dClk gene as observed experimentally. Bio-Object predicts that (1) the stability of dClk mRNA, (2) the stability of dCLK and (3) the affinity of the PER-TIM complex are determinants of the circadian duration. AVAILABILITY: The source code is available for download from http://www.tmd.ac.jp/mri/mri-end/bio-object/download/