Group I introns are structured RNAs that have been used extensively as model systems for RNA folding because they are experimentally tractable, yet complex enough to have folding challenges associated with larger RNAs. The Tetrahymena group I intron consists of a set of conserved core helices and a set of peripheral elements. Peripheral elements surround the core helices and form long range tertiary contacts between each other and to the core. Interestingly, a long-lived misfolded state is populated that has the same long range tertiary contacts as the native state but differs locally within the core. Our lab showed that the intact periphery is necessary to specify the correct core structure, as mutating tertiary contacts or removing the P5abc peripheral element dramatically destabilized the native ribozyme relative to the misfolded form. However, we also showed that the thermodynamic benefit peripheral structure provided is accompanied by kinetic liability in folding, apparently because native tertiary contacts formed by peripheral elements around the misfolded core must come apart to allow refolding of the misfolded RNA to the native state. In addition to peripheral elements, proteins also play a role in stabilizing the native structures of many group I introns. The CYT-18 protein, which occupies the same binding site as P5abc, stabilizes the functional structures of certain group I introns by using a set of insertions that are absent in other related bacterial and mitochondrial aminoacyl tRNA synthetases. Using the P5abc deletion variant of the Tetrahymena ribozyme, I sought to further define CYT-18 roles in RNA folding by probing its thermodynamic and kinetic effects on the native state formation relative to the misfolded state. I demonstrated that CYT-18, like P5abc, provided thermodynamic stability to the native state. However, unlike P5abc, CYT-18 had no apparent effect on the refolding kinetics, suggesting that a protein co-factor can stabilize the functional structure without acquiring the associated costs in RNA folding kinetics. Furthermore, I found that the mechanism of CYT-18 action appears to be distinct from P5abc. Disruption of the long-range contact P14, which is formed between P5c and L2 and is part of the network of peripheral contacts, dramatically weakened P5abc binding to the native ribozyme core by ~10⁸ fold. Interestingly, CYT-18 maintained specific and tight binding to these mutants, which suggests that CYT-18 does not rely on a circular network of contacts to specifically stabilize the native state. Instead, the specificity may arise from a more direct and intimate contact of CYT-18 with the ribozyme core. This study gives insight into an evolutionary advantage of protein co-factors in RNA folding; proteins may offer thermodynamic assistance without inhibiting folding kinetics. / text

Cette recherche vise à analyser et à comprendre le rapport qu’entretient le professeur des écoles en formation initiale avec son futur métier. En prenant appui sur la théorie structurale des représentations sociales l’objectif principal de cette recherche consiste à étudier des populations d’étudiants inscrits en 1ère année de Master MEEF (début de la formation initiale) d’une part et en 2ème année (fin de la formation initiale) d’autre part quant à leurs représentations sociales du métier auquel ils se destinent. Il convient de penser que les connaissances produites par l’analyse de ces représentations et de leur évolution au cours de la formation initiale peuvent permettre de comprendre les fondements des systèmes de pensée et d’action des professeurs des écoles qui entrent dans le métier. Cette recherche prend appui sur une pluri-méthodologie qui fait appel à deux principaux outils de recueil de données : l’entretien et le questionnaire. Les résultats obtenus montrent qu’il existe bien une représentation sociale de l’objet « métier de professeur des écoles » chez les étudiants en début de formation initiale d’une part et chez les étudiants en fin de parcours d’autre part. Ces RS font apparaître, entre les deux populations concernées, des points communs et des différences quant à leurs contenus et leurs structures. La mise en évidence d’un véritable processus de transformation de la représentation sociale du métier au cours de la formation initiale chez les sujets tend à affirmer l’existence d’une évolution de la conception du métier en termes de professionnalisation. / This study aims at analysing and understanding the relationship which the primary school teacher in initial formation, maintains with their future job. Taking support on the structural theory of the social representations, the main objective of this study consists in studying groups of students registered in 1st year of a MEEF Master’s degree (at the beginning of their initial formation) on one hand, and in 2nd year (at the end of their initial formation) on the other hand, as for their social representations of the job for which they intend themselves. It is advisable to think that the knowledge produced by the analysis of these representations and their evolution during the initial formation can allow to understand the foundations of the systems of thought and action of primary school teachers who enter the job.This study relies on a multi-methodology which exploits two main tools of data collection : the interview and the questionnaire. The results show there certainly is a social representation of the object “primary school teacher job” for students at the beginning of their initial formation on one hand and for students at the end of the formation on the other hand. These social representations show, for the two study groups, common points and differences as for their contents and their structures. The highlighting of a real transformation process of the social representation of the job during the initial formation, for the study population, tends to assert the existence of an evolution of the conception of the job in terms of professionalization.