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Impact of RNA interference on gene networks

Paper ID Volume ID Publish Year Pages File Format Full-Text
31826 44841 2006 12 PDF Available
Title
Impact of RNA interference on gene networks
Abstract

Small endogenous RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) have been found to post-transcriptionally control cellular gene networks by targeting complementary mRNAs for translation impairment (miRNA) or destruction (siRNA). We have developed a computational model, coordinated to molecular and biochemical parameters of RNA interference pathways, to provide (semi-) quantitative insight into the molecular events managing siRNA-mediated gene expression silencing in native and synthetic gene networks. Based on mass-conservation principles and kinetic rate laws, we converted biochemical RNA interference pathways into a set of ordinary differential equations that describe the dynamics of siRNA-mediated translation-regulation in mammalian cells. Capitalizing on mechanistic details of synthetic transactivator operation, we wired this model into a transcription control circuitry in which the siRNA and its target mRNA are independently regulated at the transcriptional level. In this context, we studied the impact of siRNA transcription timing on the onset of target gene transcription and production kinetics of target mRNA-encoded proteins. We also simulated the rate of siRNA-induced mRNA depletion and demonstrated that the relative concentrations of interacting siRNAs/mRNAs and the number of siRNA-specific target sites on a transcript modulate (i) the rate of target mRNA disappearance, (ii) the steady-state mRNA levels and (iii) induction dynamics of mRNA-encoded protein production. As our model predictions are consistent with available biochemical parameters, extrapolations may improve our understanding of how complex regulatory gene networks are impacted by small endogenous RNAs.

Keywords
Gene switch; Mathematical modeling; RNA silencing; SiRNA; Transcription control; Translation control
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Impact of RNA interference on gene networks
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 8, Issue 6, November 2006, Pages 672–683
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us