Title :
Integrated Circuit Modeling of Biocellular Post-Transcription Gene Mechanisms Regulated by MicroRNA and Proteasome
Author :
Alam, Shahinur ; Hasan, S. M. Rezaul
Author_Institution :
Center for Res. in Analog & VLSI Microsyst. Design (CRAVE), Massey Univ., Auckland, New Zealand
Abstract :
Regulation of gene expression stages within a cellular creature deals with all the complexities and functionalities of the organism. These genetic information processing activities inside the cell can imitate the specific operations carried out by different combinations of semiconductor devices. Appropriate gene regulation is the basis of correct system biological functionality within all living organisms. Any biochemical aberrations (mutations) in a cell cycle which are not diminished genetically can result in progressive cellular dysfunction. Controlling mutations can be approached by realizing a “silicon mimetic” electronic circuit emulating the gene expression stages. This paper presents an integrated circuit model mimicking the post-transcriptional stages in gene expression regulated by microRNAs and Proteasome. The mRNA degradation by microRNA is modeled using emitter degeneration, while the protein degradation is modeled by a mixed-signal CMOS circuit. The effect of enzymes in the degradation reaction is also explored using a “chemo-inductor.” Probabilistic analysis using Monte Carlo simulations indicates that the proposed staged gene circuit model is also robust in an environment of stochastic biochemical reactions. The model is found to be in close agreement with experimentally reported data.
Keywords :
CMOS integrated circuits; Monte Carlo methods; RNA; biochemistry; elemental semiconductors; enzymes; genetics; molecular biophysics; probability; silicon; stochastic processes; Monte Carlo simulation; Si; biocellular post-transcription gene mechanisms; biochemical aberrations; cell cycle; chemoinductor; correct system biological functionality; degradation reaction; emitter degeneration; enzyme effect; gene circuit model; gene expression regulation; gene expression stages; genetic information processing activities; integrated circuit modeling; living organisms; mRNA degradation; microRNA; mixed-signal CMOS circuit; post-transcriptional stages; probabilistic analysis; progressive cellular dysfunction; proteasome; protein degradation; semiconductor devices; silicon mimetic electronic circuit emulation; stochastic biochemical reactions; Gene circuit model; gene expression; messenger ribonucleic acid (mRNA) degradation; micro ribonucleic acid (miRNA); proteasome; protein degradation;
Journal_Title :
Circuits and Systems I: Regular Papers, IEEE Transactions on
DOI :
10.1109/TCSI.2013.2245451