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<dc:title xml:lang="fr">Développement de l'électrophorèse capillaire couplée à la spectrométrie de masse pour l'étude des modifications post-transcriptionnelles des ARN.</dc:title>
<dcterms:alternative xml:lang="en">Development of capillary electrophoresis-tandem mass spectrometry coupling for the study of post-transcriptional RNA modifications</dcterms:alternative>
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<dc:subject xml:lang="fr">Acide ribonucléique</dc:subject>
<dc:subject xml:lang="fr">Modification post-Transcriptionnelle</dc:subject>
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<dc:subject xml:lang="en">Post-Transcriptional modification</dc:subject>
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<dcterms:abstract xml:lang="fr">Les modifications post-transcriptionnelles sont fondamentales dans différents aspects pour assurer les rôles biologiques des acides ribonucléiques (ARN) dans le processus de traduction. La caractérisation chimique des modifications est par conséquent essentielle afin de permettre la compréhension des intérêts de ces modifications. Les travaux, présentés dans ce manuscrit de thèse, décrivent la mise en œuvre d’une nouvelle approche basée sur le couplage de l’électrophorèse capillaire à la spectrométrie de masse de haute résolution (CE-MS) au service de l’étude des modifications d’ARN. Ici, une stratégie sur deux niveaux a été développée. Le premier niveau d’analyse a permis de déterminer la nature des modifications présentes sur un ARN. Le second niveau, s’inspirant d’une stratégie « bottom-up », a permis de localiser les modifications sur les structures primaires des ARN. La méthodologie développée a permis de caractériser, sans ambiguïté, un grand nombre de modifications sur différents types d’ARN et notamment des ARN de transfert, ouvrant la voie à la CE-MS comme un nouvel outil d’analyse pour la caractérisation de modifications d’ARN.</dcterms:abstract>
<dcterms:abstract xml:lang="en">Post-transcriptional modifications are fundamental in different aspects to ensure the biological roles of ribonucleic acids (RNA) in the translation process. The chemical characterization of the modifications is therefore essential in order to understand their influences. The work presented in this thesis manuscript describes the implementation of a new approach based on the coupling of capillary electrophoresis to high resolution mass spectrometry (CE-MS) for the investigation of RNA modifications. Here, a two-level strategy has been developed. The first level of analysis enable to determine the nature of the modifications contained on an RNA. The second level of this strategy, inspired by the "bottom-up" approach, permit to map the modifications onto the primary structures of RNA. The methodology developed allows to characterize, without ambiguity, a large number of modifications on different types of RNA and particularly on transfer RNA, paving the way to CE-MS as a new analysis tool for the characterization of RNA modifications.</dcterms:abstract>
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