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Etude sur le complexe TAR/Tat/cycline T1 Et Etude des régulations de l'épissage de l'ARN pré-messager du virus HIV-1 : effet global des protéines virales et analyse fine du rôle des protéines SR ASF/SF2 et 9G8 au site accepteur A3

Abstract : This work of thesis contained two different parts : the one concerns the study of the TAR/Tat/cycline T1 complex involved in the transactivation of the transcription of the HIV-1 RNA, the other one concerns various facets of the regulation of the splicing of the HIV-1 RNA. The interaction of the viral protein Tat with the TAR element present in the 5 ' extremity of the HIV-1 RNA on one hand, and the cycline T1, composing of the complex p-TEFb responsible for the hyperphosphorylation of the RNA polymerase II on the other hand, is essential to obtain viral RNA of full length. In the objective to realize a structural study of the complex TAR/Tat/cycline T1, TAR RNA and a fragment of the cycline T1 were produced in appropriate quantities. Numerous attempts of complexation of three partners (TAR, Tat and cycline T1) were made, but the quality of crystals was not sufficient for a radiocristallographic study of the complex. Splicing is a major stage of the cycle of reproduction of the virus HIV-1. His RNA contains 5 donor splice sites and 8 acceptor splice sites whose combined use allows the production 9 viral ORF. The variations of the alternative épissage of HIV-1 RNA according to the expression of viral proteins Tat and Rev were studied. We besides studied the effect of proteins SR on the use of acceptor splice sites A2 and A3. The fine study of the regulating element ESEt of the site A3 revealed the involvement of the SR protein 9G8 in the complex regulation of this site.
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https://hal.univ-lorraine.fr/tel-01748196
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  • HAL Id : tel-01748196, version 1

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Jean-Michel Saliou. Etude sur le complexe TAR/Tat/cycline T1 Et Etude des régulations de l'épissage de l'ARN pré-messager du virus HIV-1 : effet global des protéines virales et analyse fine du rôle des protéines SR ASF/SF2 et 9G8 au site accepteur A3. Biologie moléculaire. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10151⟩. ⟨tel-01748196⟩

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