Biais de composition nucléotidique des gènes et épissage alternatif

Abstract : Splicing, a major step in gene expression, consists in the removal of the introns and the production of mature transcripts or mRNA. The regulation of or the disturbances in splicing are involved in numerous physiopathological situations. In this work, I used and analysed with bio-informatic approaches a lot of genome-wide datasets in order to define better the rules governing exon recognition during the splicing step. I show in this work that the mechanisms of exon recognition depend on the nucleotidic composition bias of the genes which host these exons. Thus, the recognition of the exons located in genes enriched with guanine and cytosine essentially depends on their 5' splicing site, which can be hidden by secondary structures. The recognition of the exons located in genes enriched with thymine and adenine essentially depends on splicing signals placed upstream the exons. Moreover, I show that the chromatin organization varies according to the nucleotidic composition bias in the genes, and that it has a particular impact on exon recognition. A lot of studies have shown that the genes are not randomly organized in a genome and that the architecture of the genes and of the chromosomes depends on their nucleotidic composition. Put together, my work suggests that it exists an direct link between the nucleotidic composition of a genomic region, the chromatin architecture and the recognition of the exons during the splicing step.
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https://tel.archives-ouvertes.fr/tel-02275819
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Submitted on : Monday, September 2, 2019 - 1:29:24 AM
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Sébastien Lemaire. Biais de composition nucléotidique des gènes et épissage alternatif. Bio-Informatique, Biologie Systémique [q-bio.QM]. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSEN005⟩. ⟨tel-02275819⟩

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