Caractérisation structurale et fonctionnelle de la ribonucléoparticule 7SK chez les eucaryotes supérieurs

par Sylvain Egloff

Thèse de doctorat en Biologie - Santé. Biotechnologie

Sous la direction de Tamás Kiss.

Soutenue en 2005

à Toulouse 3 .

  • Titre traduit

    Structural and functional characterization of the ribonucléoparticule 7SK small nuclear ribonucleoparticle


  • Pas de résumé disponible.


  • Résumé

    In eucaryotic cells, the positive transcription elongation factor b (P-TEFb) stimulates elongation of transcription by phosphorylating the carboxy-terminal domain of the largest subunit of RNA polymerase II (pol II), allowing synthesis of full-length messenger RNAs. 7SK small nuclear RNA (snRNA), together with HEXIM proteins, functions as a regulator of P-TEFb by inhibiting its protein kinase activity. 7SK snRNA interacts with both P-TEFb and HEXIM1 and thereby, sequesters P-TEFb into a large kinase-inactive complex. We identified the functionally important elements of human 7SK snRNA required for in vivo binding of HEXIM1 and P-TEFb. We demonstrated that binding of HEXIM1 is directed by an element located in the 5'-terminal hairpin of 7SK snRNA. In contrast, two distinct regions, the 5'-terminal hairpin and the short 3'-terminal hairpin, are required for recruitment of P-TEFb. A minimal 7SK snRNA, carrying all the elements important for binding of HEXIM and P-TEFb, can inhibit pol II transcription in HeLa cells. Thus, we identified all the elements of 7SK snRNA necessary for inhibition of transcription elongation by pol II in living cells. In HeLa cells, roughly half of P-TEFb is sequestered in an inactive state within the 7SK snRNA. However, this population of P-TEFb can be rapidly dissociated from 7SK upon treatment of cells with stress-inducing agents. We identified an internal hairpin region of 7SK snRNA that seems to be important for the release of P-TEFb from 7SK. Finally, we purified and identified new proteins that could be part of the 7SK ribonucleoparticle.

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La version de soutenance existe sous forme papier

Informations

  • Détails : 1 vol. ( 162 f.)
  • Notes : Publication autorisée par le jury
  • Annexes : Bibliogr. f. 130-161

Où se trouve cette thèse ?

  • Bibliothèque : Université Paul Sabatier. Bibliothèque universitaire de sciences.
  • Disponible pour le PEB
  • Cote : 2005TOU30143
Voir dans le Sudoc, catalogue collectif des bibliothèques de l'enseignement supérieur et de la recherche.