Simplified stochastic models with time delay for studying the degradation process of mRNA molecules

Message RNA (mRNA) is the template for protein synthesis. It carries information from DNA in the nucleus to the ribosome sites of protein synthesis in the cell. The turnover process of mRNA is a chemical event with multiple small step reactions and the degradation of mRNA molecules is an important step in gene expression. A number of mathematical models have been proposed to study the dynamics of mRNA turnover, ranging from a one-step first order reaction model to the linear multi-component models. Although the linear multi-component models provide detailed dynamics of mRNA degradation, the simple first-order reaction model has been widely used in mathematical modelling of genetic regulatory networks. To illustrate the difference between these models, we first considered a stochastic model based on the multi-component model. Then a simpler stochastic model was proposed to approximate the linear multi-component model. We also discussed the delayed one-step reaction models with different types of time delay, including the constant delay, exponentially distributed delay and Erlang distributed delay. The comparison study suggested that the one-step reaction models failed to realise the dynamics of mRNA turnover accurately. Therefore, more sophisticated one-step reaction models are needed to study the dynamics of mRNA degradation.

[1]  D. Gillespie Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[2]  J. Hasty,et al.  Translating the noise , 2002, Nature Genetics.

[3]  Rui Zhu,et al.  Validation of an algorithm for delay stochastic simulation of transcription and translation in prokaryotic gene expression , 2006, Physical biology.

[4]  B. Moritz,et al.  Degradation of hsp70 and Other mRNAs in Drosophila via the 5′–3′ Pathway and Its Regulation by Heat Shock* , 2007, Journal of Biological Chemistry.

[5]  Roy Parker,et al.  Computational Modeling and Experimental Analysis of Nonsense-Mediated Decay in Yeast , 2003, Cell.

[6]  A. van Hoof,et al.  Messenger RNA regulation: to translate or to degrade , 2008, The EMBO journal.

[7]  K. Burrage,et al.  Stochastic delay differential equations for genetic regulatory networks , 2007 .

[8]  Jeffrey Wilusz,et al.  The highways and byways of mRNA decay , 2007, Nature Reviews Molecular Cell Biology.

[9]  A. Oudenaarden,et al.  Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences , 2008, Cell.

[10]  Jane Hillston,et al.  Modelling co-transcriptional cleavage in the synthesis of yeast pre-rRNA , 2008, Theor. Comput. Sci..

[11]  R Parker,et al.  Computational modeling of eukaryotic mRNA turnover. , 2001, RNA.

[12]  Nacho Molina,et al.  Mammalian Genes Are Transcribed with Widely Different Bursting Kinetics , 2011, Science.

[13]  J. Matis,et al.  Compartmental models with Erlang distributed residence times and random rate coefficients , 1992 .

[14]  K. Burrage,et al.  Binomial leap methods for simulating stochastic chemical kinetics. , 2004, The Journal of chemical physics.

[15]  Vassily Hatzimanikatis,et al.  The Origins of Time-Delay in Template Biopolymerization Processes , 2010, PLoS Comput. Biol..

[16]  J. Paulsson,et al.  Effects of Molecular Memory and Bursting on Fluctuations in Gene Expression , 2008, Science.

[17]  E. Blackburn,et al.  Telomere states and cell fates , 2000, Nature.

[18]  Chris Cornelis,et al.  Modelling gene and protein regulatory networks with Answer Set Programming , 2011, Int. J. Data Min. Bioinform..

[19]  N. Monk Oscillatory Expression of Hes1, p53, and NF-κB Driven by Transcriptional Time Delays , 2003, Current Biology.