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Modeling the effects of SR proteins on alternative splicing

Damien Eveillard 1 Delphine Ropers 2 Hidde de Jong 3 Christiane Branlant 2 Alexander Bockmayr 1
1 MODBIO - Computational models in molecular biology
INRIA Lorraine, LORIA - Laboratoire Lorrain de Recherche en Informatique et ses Applications
3 VASY - System validation - Research and applications
Inria Grenoble - Rhône-Alpes, LIG - Laboratoire d'Informatique de Grenoble
Abstract : Alternative splicing is a biological process occurring in post transcriptional regulation. Through the elimination of selected introns, alternative splicing makes it possible to generate several kinds of mRNA. The combinatorial effect of splicing contributes to biological diversity, especially in the case of the human immunodeficiency virus (HIV). Recent biological studies show the impact that SR proteins have on the dynamics of post-transcriptional regulation by controlling the splicing process. SR proteins can be divided into two functional classes: they may either activate or inhibit splicing. Our goal is to incorporate this biological factor into a global model of HIV in order to better understand the dynamics of the virus. Due to the complexity of the regulation of alternative splicing, the knowledge that can be gained from experiments is limited. Each experiment studies only one splicing site. In a first approach, we model SR regulation in this restricted context. Using differential equations, we develop a qualitative model for the A3 splicing site in HIV. The qualitative behavior depends on the values of the reaction kinetics parameters. Experimental results available to us validate this first approach in the equilibrium state. Our second approach aims at a validation on a higher scale. The goal is to obtain a qualitative model that can be validated both on the scale of a single splicing site and on the scale of the whole HIV, in order to represent the global effect of alternative splicing in the HIV cycle.
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Submitted on : Tuesday, September 26, 2006 - 2:55:09 PM
Last modification on : Friday, February 4, 2022 - 3:24:10 AM


  • HAL Id : inria-00101060, version 1


Damien Eveillard, Delphine Ropers, Hidde de Jong, Christiane Branlant, Alexander Bockmayr. Modeling the effects of SR proteins on alternative splicing. [Intern report] A02-R-117 || eveillard02b, 2002, 8 p. ⟨inria-00101060⟩



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