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Analyse structurale et fonctionnelle de la région des A-repeats de l'ARN Xist impliqué dans l'inactivation du chromosome X dans les mammifères femelles

Abstract : X-chromosome inactivation is the transcriptional silencing of one of the two X chromosomes in female mammal cells. This mechanism of dosage compensation ensures an equal level of the X-linked genes expression between males (XY) and females (XX). It initiates with the accumulation of the Xist RNA (X inactive specific transcript) on the futur inactive X chromosome (Xi). It is followed by the apposition of epigenetic marks such as histone modifications, that ensure establishment, maintenance and transmission of the inactive state of the chromatin. Xist RNA comprises a number of repeated regions and, in particular to its 5' end the A region, absolutely necessary for the establishment of the X-inactivation. My research was focused on the study of this singular region: its structure and its protein interactions. The FRET method (Fluorescence Resonance Energy Transfer) applied to RNA allowed us to ascertain that the RNA is structured in two long stem-loop structures each including four repeats. In a second part, I characterized the in vitro interaction of this region with some of its protein partners. The A region interacts directly with PTB, KSRP and ASF/SF2 proteins. The first two proteins may have a role in RNA stability whereas ASF/SF2 could be involved in the splicing process
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Anne Savoye. Analyse structurale et fonctionnelle de la région des A-repeats de l'ARN Xist impliqué dans l'inactivation du chromosome X dans les mammifères femelles. Biochimie, Biologie Moléculaire. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0354⟩. ⟨tel-01749664⟩

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