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Approche plurielle a l'etude de la structure tertiaire de l'ARN chez les virus

Posted on:2008-09-29Degree:Ph.DType:Thesis
University:Universite de Montreal (Canada)Candidate:Permal, EmmanuelleFull Text:PDF
GTID:2442390005971494Subject:Biology
Abstract/Summary:PDF Full Text Request
The study of RNA macromolecule structure is essential to understand genetic expression and to explore the plural role of RNA. To give some clues on the virus's ability to recruit the cellular machinery of the host, we investigated the 3D structure of some elements of their genome. Their genomic and structural analysis is crucial for the identification of novel drug target and for the eradication of the corresponding disease. In this thesis, the focus is made on RNA motifs, that are recurrent building block of the RNA 3D structure, and their use in viral RNA. Our hypothesis of work is that RNA motifs confer the function to the RNA molecule. Therefore, their identification and localization is useful for the understanding of how viruses work. We present three approaches in this thesis: (i) viral element building using 3D RNA homology modeling; (ii) the characterization of an ubiquitous viral RNA motif; (iii) the annotation of numerous viral elements given their RNA motif composition. The number of available 3D structure has increased in databases since the ribosomal RNA subunit crystal structure was solved in 2000. We used more than 3000 RNA structures during our research. To achieve our goals, we developed many processi combined with bioinformatics tools allowing RNA structure analysis (annotation, molecular modeling, motif search...). The first aspect of this work concerns the property of tridimensional structure conservation between different viruses. To predict the tertiary structure of the RNA, a homology modeling pipeline was developed and gave four new 3D structural models of the viral stem-loop D, a highly conserved element wihin picomaviridae. The second aspect reveals the peculiar organization of an RNA motif: the GC quartet. It was characterized and searched in the PDB database (Protein DataBank) leading to its description as a ubiquitous stabilizing structural motif. The third aspect concerns the redundancy of the RNA motif. A broad study characterizing the viral elements was realized, highlighting the unique feature of bulge motifs and providing the first catalogue of viral RNA elements annotated with their intrinsic motifs. During this study, it appears clearly that viral elements constitute an excellent model choice to analyze the RNA structure as they possessed numerous interesting motifs In addition, we could observe the redundancy of some motifs and, in the contrary, the specificity of others. Those last ones, that represent the identity of each element studied, could be used in the design of new drugs as targets.;Key words: Bioinformatics, Modeling, motif detection, structure, virus, RNA, RNA motifs.
Keywords/Search Tags:RNA, Structure, Modeling
PDF Full Text Request
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