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Etude expérimentale du rôle des protéines SR dans la régulation de l'épissage de l'ARN du virus HIV-1, responsable de l'immunodéficience humaine, et modélisation mathématique de ces régulations

Abstract : Splicing is a key step for virus HIV-1 multiplication. Four donor and eight acceptor splicing sites are used in combinaison to produce about 40 mRNAs. We showed that the acceptor sites A1 to A5 are differentially regulated by the SR proteins ASF/SF2, SC35, 9G8 and SRp40 (regulator of cellular splicing). Our deep study of the regulation at site A3 shows the presence of a splicing activatory element, ESEt, that binds both the SC35 and ASF/SF2 proteins. We also showed that protein SC35 binds the ESS2 inhibitory element, and compete protein hnRNP A1 for binding to this site. We showed that regulation of site A3 by the SR proteins is conserved in SIVcpz virus and HIV-1. Based on our experimental results, mathematical models simulating splicing regulations at site A3 and competition of the A3-A7 sites, respectively, were established by the team of A. Bockmayr (LORIA, Nancy).
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Delphine Ropers. Etude expérimentale du rôle des protéines SR dans la régulation de l'épissage de l'ARN du virus HIV-1, responsable de l'immunodéficience humaine, et modélisation mathématique de ces régulations. Biochimie, Biologie Moléculaire. Université Henri Poincaré - Nancy 1, 2003. Français. ⟨NNT : 2003NAN10177⟩. ⟨tel-01748098⟩

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