Дисертації з теми "TRNA Structure"
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Boonyalai, Nonlawat. "Lysyl-tRNA synthetase : structure-function studies." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429379.
Повний текст джерелаLorber, Bernard. "Contribution a l'etude du systeme aspartyl-trna synthetase-trna**(asp) chez la levure saccharomyces cerevisiae." Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13049.
Повний текст джерелаSwinehart, William E. Jr. "A Biochemical Investigation of Saccharomyces cerevisiae Trm10 and Implications of 1-methylguanosine for tRNA Structure and Function." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429867956.
Повний текст джерелаNassar, Nicolas. "Structure de la seryl-tRNA synthétase de Escherichia coli à 2. 5 [angström] de résolution." Grenoble 1, 1992. http://www.theses.fr/1992GRE10162.
Повний текст джерелаAgyeman, Akwasi. "T box antiterminator-tRNA recognition elements /." View abstract, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3266062.
Повний текст джерелаDesogus, Gianluigi. "Structural studies of lysyl-tRNA synthetases and DNA primases." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369258.
Повний текст джерелаMejdoub, Hafedh. "Aspartyl-trna synthetase cytoplasmique de levure : structure primaire et domaines accessibles." Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13042.
Повний текст джерелаMejdoub, Hafedh. "Aspartyl-tRNA synthétase cytoplasmique de levure structure primaire et domaines accessibles /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37608053w.
Повний текст джерелаCacan, Ercan. "Evolutionary synthetic biology: structure/function relationships within the protein translation system." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45838.
Повний текст джерелаPerreau, Victoria M. "Genomic organisation and structure of a novel seryl-tRNA from Candida albicans." Thesis, University of Kent, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242889.
Повний текст джерелаTakita, Teisuke. "The Structure and Functions of the Lysyl-tRNA Synthetase of Bacillus stearothermophilus." Kyoto University, 1996. http://hdl.handle.net/2433/78070.
Повний текст джерела0048
新制・課程博士
博士(農学)
甲第6479号
農博第892号
新制||農||720(附属図書館)
学位論文||H8||N2923(農学部図書室)
UT51-96-F358
京都大学大学院農学研究科食品工学専攻
(主査)教授 外村 辨一郎, 教授 左右 田健次, 教授 佐々木 隆造
学位規則第4条第1項該当
Garcia-Brugger, Angela. "Contribution a l'etude de la structure tertiaire des trna et interaction avec les aminoacyl-trna synthetases. Utilisation de sondes chimiques et analyse de variants du trna#a#s#p de levure." Strasbourg 1, 1990. http://www.theses.fr/1990STR13120.
Повний текст джерелаFrandsen, Jane K. "Non-canonical T box riboswitch-tRNA recognition in ileS variants." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1560863957375393.
Повний текст джерелаZhang, Wenhua. "Structural Basis of the Biosynthesis of the tRNA N6-threonylcarbamoyladenosine." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114851/document.
Повний текст джерелаMost tRNAs undergo chemical modifications during their maturation after the transcription. N6-threonylcarbamoyladenosine (t6A) is universally present at position 37 of tRNAs that recognize ANN-codons. tRNA t6A plays an essential role in translational fidelity through enhancing the codon-anticodon interaction. Recently, the tRNA t6A-modifying enzymes have been identified and characterized in bacteria, archaea and yeast. The biosynthesis of tRNA t6A proceeds in two main steps: first, the biosynthesis of an unstable intermediate threonylcarbamoyladenylate (TCA) by Sua5/YrdC family protein, using ATP, L-threonine, bicarbonate as substrates; second, the transfer of threonylcarbamoyl-moiety from TCA onto A37 of cognate tRNAs by a set of other proteins that use Kae1/Qri7/YgjD family proteins as a catalytic component. Though the biosynthesis of tRNA t6A could be accomplished by Sua5 and Qri7 in yeast mitochondria, the t6A biosynthesis in archaea and yeast cytoplasm requires Sua5 and KEOPS protein complex, which consists of Kae1, Bud32, Cgi121, Pcc1 in archaea, and a fifth Gon7 in yeast. In bacteria, it requires YrdC, YgjD, YeaZ and YjeE, of which YeaZ and YjeE are not related to any KEOPS subunits. Presently, the molecular mechanism of Sua5/YrdC in catalyzing the TCA biosynthesis is not well understood; How the KEOPS subunits assembly and cooperatively transfer threonylcarbamoyl-moiety from TCA to tRNA is not known; The contribution of YeaZ and YjeE in t6A biosynthesis in bacteria still remains to be probed.In this study, we report crystal structures of P. abyssi Sua5, S. cerevisiae Gon7/Pcc1 and Bud32/Cgi121 binary complexes, and E. coli YgjD-YeaZ heterodimer. Based on the information revealed by the crystal structures, advanced biochemical characterizations were carried out to validate the hypotheses. We confirm first that Sua5/YrdC is capable of catalyzing the TCA biosynthesis using substrates of ATP, L-threonine, and bicarbonate. The structure of P. abyssi Sua5 in complex with pyrophosphate provides a basis for its ATP-pyrophosphatase activity. Second, the structure of Gon7 reveals that it functions as a structural mimic of Pcc1 and therefore prevents the formation of Pcc1 homodimer, which mediates the formation of a dimer of tetrameric KEOPS from archaea. The structure of Bud32-Cgi121 in complex with ADP provides a basis in support of the dual kinase and ATPase activities of Bud32. We present a structural model of yeast KEOPS that exists as a heteropentamer. Third, we discovered that the weak intrinsic ATPase activity of YjeE is activated by YgjD-YeaZ heterodimer. YgjD, YeaZ and YjeE associate and form a ternary complex that is regulated by both the formation of YgjD-YeaZ heterodimer and the binding of ATP to YjeE. The model of YgjD-YeaZ-YjeE ternary complex provides structural insight into the essential role of YeaZ and YjeE in t6A biosynthesis in bacteria. This work provides structural insights into understanding the biosynthesis of tRNA t6A that is essential and ubiquitous in all three domains of life
McCormack, John Crisler. "An internal tRNA-like structure regulates the life cycle of a plus-sense RNA virus." College Park, Md.: University of Maryland, 2007. http://hdl.handle.net/1903/7768.
Повний текст джерелаThesis research directed by: Dept. of Cell Biology and Molecular Genetics . Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
Zhang, Deqiang Roberts Richard W. Goddard William A. "Structure-based design of mutant proteins : I. Molecular docking studies of amino acid binding to wild-type aminoacyl-tRNA synthetases. II. Structure-based design of mutant aminoacyl-tRNA synthetases for non-natural amino acid incorporation /." Diss., Pasadena, Calif. : California Institute of Technology, 2003. http://resolver.caltech.edu/CaltechETD:etd-12182002-190040.
Повний текст джерелаJühling, Frank. "Structure and evolution of animal mitochondrial tRNAs." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ012.
Повний текст джерелаThe bioinformatic approaches presented in this thesis include the development of databases for classical tRNAs and the mitochondrial tRNAs of metazoans. They are based on new tools for the detection of "bizarre" tRNA genes and sequences, and for the calculation of alignments based on their structural features. The analysis of collected sequences have led to an global overview on the diversity of tRNAs in mitochondrial genomes covering all taxonomic groups of metazoans, but also to a better understanding of genome organization and their evolution. The present study revealed the existence of the smallest known tRNA so far and provides the basis for understanding the three-dimensional folding of mitochondrial tRNA. This work helps to better understand the structure/function relationships of human mitochondrial tRNAs and, in particular, the dysfunctions in mitochondrial pathologies
Somme, Jonathan. "Structure-function relationship studies on the tRNA methyltransferases TrmJ and Trm10 belonging to the SPOUT superfamily." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209122.
Повний текст джерелаIn the first part of this work we have identified the TrmJ enzyme of Sulfolobus acidocaldarius (the model organism of hyperthermophilic Crenarchaeota) which 2’-O-methylates the nucleoside at position 32 of tRNAs. This protein belongs to the SPOUT superfamily and is homologous to TrmJ of the bacterium Escherichia coli. A comparative study shows that the two enzymes have different specificities for the nature of the nucleoside at position 32 as well as for their tRNA substrates. To try to understand these shifts of specificity at a molecular level we solved the crystal structure of the SPOUT domains of the two TrmJ proteins.
In the second part of this work, we have determined the crystal structure of the Trm10 protein of S. acidocaldarius. This is the first structure of a 1-methyladenosine (m1A) specific Trm10 and also the first structure of a full length Trm10 protein. The Trm10 protein of S. acidocaldarius is distantly related to its yeast homologues which are 1-methylguanosine (m1G) specific. To understand the difference of activity between the Trm10 enzymes, we compared the yeast and the S. acidocaldarius Trm10 structures. Remarkably several Trm10 proteins (such as Trm10 of Thermococcus kodakaraensis) are even able to form both m1A and m1G. To understand the capacity of the T. kodakaraensis protein to methylate A and G, a mutational study was initiated./Lors de la traduction, les ARN de transfert (ARNt) jouent le rôle crucial d’adaptateurs entre l’ARN messager et les acides aminés. Les ARNt sont transcrits sous forme de pré-ARNt qui doivent être maturés. Lors de cette maturation, plusieurs nucléosides sont modifiés. Un grand nombre de ces modifications sont des méthylations des bases ou du ribose. Quatre familles d’ARNt méthyltransferases sont actuellement connues, dont la superfamille des SPOUT. Les membres de cette superfamille sont caractérisés par un nœud dans la chaîne polypeptidique du côté C-terminal. C’est au niveau de ce nœud que se lie la S-adénosylméthionine qui est le donneur de groupement méthyle. A l’exception de Trm10 qui est monomérique, toutes les protéines SPOUT connues sont dimériques et leur site actif est formé de résidus provenant des deux protomères. Selon l’espèce, une même modification peut être formée à la même position dans la molécule d’ARNt par des enzymes qui appartiennent à des familles différentes. A l’opposé, des enzymes homologues peuvent présenter des spécificités ou des activités différentes.
Au cours de ce travail, nous avons identifié l’enzyme TrmJ de Sulfolobus acidocaldarius (l’organisme modèle des Crénarchées hyperthermophiles) qui méthyle le ribose du nucléoside en position 32 des ARNt. Cette protéine est un homologue de l’enzyme TrmJ de la bactérie Escherichia coli. L’étude comparative que nous avons réalisée a révélé que ces deux enzymes présentent une différence de spécificité pour la nature du nucléoside en position 32 ainsi que pour les ARNt substrats. Afin de comprendre ces différences de spécificité au niveau moléculaire, les structures des domaines SPOUT des deux TrmJ ont été déterminées et comparées.
En parallèle, nous avons résolu la structure cristalline de la protéine Trm10 de S. acidocaldarius. C’est la première structure disponible d’un enzyme Trm10 formant de la 1-méthyladénosine (m1A). C’est aussi la première structure complète d’une protéine Trm10. Les enzymes homologues des levures Saccharomyces cerevisiae et Schizosaccharomyces pombe qui n’ont que peu d’identité de séquence avec l’enzyme de S. acidocaldarius, forment de la 1-méthylguanosine (m1G). Dans le but de comprendre comment ces enzymes homologues peuvent présenter des activités différentes, leurs structures ont été comparées. De manière surprenante, certains homologues de Trm10 (comme l’enzyme de l’Euryarchée Thermococcus kodakaraensis) sont capables de former du m1A et du m1G. Afin de mieux comprendre comment ces protéines sont capables de méthyler deux types de bases, nous avons initié l’étude de l’enzyme Trm10 de T. kodakaraensis par mutagenèse dirigée.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Wintz, Henri. "Contribution à l'étude de l'organisation et de la structure des gènes de tRNA mitochondriaux des plantes." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb376192427.
Повний текст джерелаBeauvallet, Christian. "Resolution de la structure primaire d'oligopeptides et de polypeptides : bilan et perspectives." Paris 6, 1988. http://www.theses.fr/1988PA066049.
Повний текст джерелаKernel, landine. "Structure en solution de macromolécules chargées dans de fortes concentrations de sels : étude de l'ARNtPhe de levure et de la malate déshydrogénase d'Haloarcula marismortui." Université Joseph Fourier (Grenoble), 1997. http://www.theses.fr/1997GRE10021.
Повний текст джерелаRudinger-Thirion, Joëlle. "Contribution a l'etude de la reaction d'aminoacylation de trna et pseudo-trna. Relations structure/fonction entre les systemes specifiques de l'acide aspartique, de l'histidine et de la valine." Université Louis Pasteur (Strasbourg) (1971-2008), 1992. http://www.theses.fr/1992STR13069.
Повний текст джерелаSenger, Bruno. "Etude de nouveaux aspects liés à la machinerie traductionnelle : amidotransférases et aminoacyl-ARNt synthétases." Habilitation à diriger des recherches, Université Louis Pasteur - Strasbourg I, 2006. http://tel.archives-ouvertes.fr/tel-00270801.
Повний текст джерелаChez la levure, il existe un complexe multi-synthétasique simplifié formé de la MetRS, la GluRS et Arc1p, une protéine dont le gène est en interaction non seulement avec la machinerie de transport nucléocytoplasmique mais également celle de la biosynthèse des ARNts. Ces découvertes m'ont amené à étudier le rôle de Mtr10p dans les échanges nucléocytoplasmiques et un possible lien avec le transport des ARNts. Les acquis lors de ces travaux auront été utiles dans l'étude du rôle d'Efl1p, une GTPase de type EF-2 impliquée dans une étape tardive (cytoplasmique) de la biogenèse de la grande sous-unité ribosomale 60S.
Grâce aux travaux antérieurs, j'ai pu me familiariser avec de nombreuses techniques biochimiques et génétiques qui s'avèreront précieuses pour mon projet d'étude de la localisation et de l'interactome des aminoacyl-ARNt synthétases (aaRS). En effet, il n'est pas concevable que le couple ARNt/aaRS évolue de façon autonome dans la cellule mais il doit interagir / communiquer d'une part avec les acteurs directs de la synthèse protéique et, d'autre part, avec des facteurs intervenant dans d'autres processus cellulaires. Trouver, comprendre et étudier les spécificités de divers organismes fournira peut-être de nouvelles pistes à but thérapeutique restées insoupçonnées jusqu'alors.
Un autre aspect de mon projet, toujours relié aux aaRS, traitera d'un système atypique de la machinerie traductionnelle qui est celui des voies de formation des aminoacyl-ARNts dans les systèmes asparagine et glutamine. En effet, un certain nombre d'organismes, pathogènes de l'homme, ne possèdent pas d'aaRS (AsnRS, GlnS) pour l'un et/ou l'autre de ces acides aminés et pallient à cette absence par l'utilisation d'une voie indirecte pour la formation de ces aminoacyl-ARNts. L'étude de ces voies est non seulement intéressante sur les plans évolutifs et relation structure-fonction ARN-protéine mais également d'un point de vue appliqué, certes à plus long terme, dans le but d'enrayer ces voies de biosynthèse amenant ainsi des cibles alternatives pour des molécules de type antibiotique. Cet aspect est d'autant plus important qu'à l'heure actuelle apparaissent des phénomènes de résistance aux antibiotiques posant de vrais problèmes de santé publique.
Yousef, Mary Roneh. "Characterization of the in vitro interaction between bacillus subtilis glyQS T Box leader RNA and tRNA(Gly)." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1103744744.
Повний текст джерелаTitle from first page of PDF file. Document formatted into pages; contains xv, 139 p.; also includes graphics (some col.) Includes bibliographical references (p. 123-139).
Joshi, Rajiv L. "Régions "tRNA-Like" des RNA de virus végétaux structure, reconnaissance par des protéines spécifiques, recherche d'une fonction." Grenoble 2 : ANRT, 1986. http://catalogue.bnf.fr/ark:/12148/cb375985518.
Повний текст джерелаLeite, Ney Ribeiro. "Estudos moleculares de duas triptofanil tRNA sintetases do parasita Leishmania major e de uma cisteíno protease da bactéria Xylella fastidiosa." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-08092007-163023/.
Повний текст джерелаThe aminoacyl tRNA synthetases (aaRSs) are essential enzymes in protein synthesis that ensure the correct match between amino acids and their cognate tRNAs. The mitochondrial (kinetoplast) genome of trypanossomatids lacks tRNA genes, and therefore nucleus-encoded tRNAs are imported from the cytoplasm, the kinetoplast genetic code deviates from the universal code in that UGA instead of UGG encodes for tryptophan. A single nucleus-encoded tRNATrp(CCA) is responsible for Trp insertion during organellar protein synthesis. To decode both Trp codons (UGA and UGG), tRNATrp(CCA) undergoes a single C to U editing event at position 34 of the anticodon yielding to versions of the tRNA in the mitochondria with anticodon CCA and UCA, permitting UGA decoding. This work have characterized two Leishmania major tryptophanyl-tRNA synthetase, acording western blotting experiments and ?in silico? sequence analisis one of cytoplasmatic localization (LmTrpRS1) and another from mitochondria localization (LmTrpRS2). The mature mRNA transcripts for both genes were defined by 5? and 3? RT-PCR. Both enzymes were cloned into several expressions vectors. LmTrpRs1 was obtained as an insoluble protein and LmTrpRs2 expressed into the soluble fraction in pET28a expression system. LmTrpRS2 protein, however, is unstable precipitating shortly after purification. The enzymatic assay showed that this enzyme is able to recognize both tRNATrp. Molecular modeling for LmTrpRS1 and LmTrpRS2 were constructed using the cytoplasmatic human tryptophanyl tRNA synthetase as a model, to study the interaction between proteins and tRNATrp. Xylella fastidiosa is a xylem-limited, gram-negative bacteria responsible for a large number of economically important plant diseases, such as Pierces disease in grapevines, citrus variegated chlorosis (CVC) in sweet oranges and leaf scorch diseases in other plants, including almond, plum, oleander, mulberry and coffee. In all cases, X. fastidiosa infects the plant xylem and impairs fruit production. Here, we report the crystal structure of xylellain, a cystein protease from X. fastidiosa. The structure was solved by single-wavelength anomalous dispersion (SAD) using seleno-methionine containing xylellain crystals. The final structure of Xylellaína was refined against the best native data set (1.65 Å) showing R/Rfree= 17/21. Xylellain shares fold similar to Papain like Family, but contains some interesting features, like a 38 N-terminal tail covering the active site cleft; one intriguing ribonucleotide found outside the active site and one loop that resemble the ocluding loop from cathepsin B.
Jühling, Tina. "ARNt "manchots" : structure, fonctionnalité et évolution." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ119/document.
Повний текст джерелаTRNAs are adapter molecules linking the genetic information of messenger RNAs with the primary amino acid sequence of proteins. tRNAs have a typical cloverleaf-like secondary structure. Some mitochondrial tRNAs show a high derivation from this canonical tRNA structure. An extreme case of structural truncations can be observed in mitochondria of the nematode R. culicivorax. This study aims the functional characterization of such “bizarre” tRNAs in defining their structural properties and their functionality with interacting partner proteins such as CCA-adding enzymes and aminoacyl-tRNA synthetases. This work reveals that armless tRNAs form a hairpin-shaped secondary structure. 3D structures exhibit a high intrinsic flexibility. Initial tests could not demonstrate aminoacylation activity. However, armless tRNAs represent functional molecules for CCA-incorporation, indicating adaptations of CCA-adding enzymes to armless tRNAs
ZHAO, JING. "EFFECTS OF LOCAL RNA SEQUENCE AND STRUCTURAL CONTEXTS ON RIBONUCLEASE P PROCESSING SPECIFICITY." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554396751955631.
Повний текст джерелаDufour, Emmanuelle. "Interaction de la transcriptase inverse de HIV-1 avec son tRNA amorce : études biochimiques et détermination du site de liaison de l'enzyme à l'extrémité 3' du tRNA-Lys3." Bordeaux 2, 1997. http://www.theses.fr/1997BOR28523.
Повний текст джерелаMadore, Éric. "Étude des interactions entre le tRNA[exposant G] [exposant L] [exposant U] et la glutamyl-tRNA synthétase chez Escherichia coli, rôles des bases modifiées, structure des formes inactive et dimérique du tRNA[exposant G] [exposant L] [exposant U] et identification des sites de contacts." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0004/NQ43089.pdf.
Повний текст джерелаNadal, i. Matamala Anna. "El virus de l'hepatitis C i la ribonucleasa Phumana: aspectes biològics i terapèutics." Doctoral thesis, Universitat de Girona, 2004. http://hdl.handle.net/10803/7630.
Повний текст джерелаS'han estudiat dos models d'RNasa P, la RNasa P humana guiada per seqüència guia externa (EGS) i l'RNA M1 de l'RNasa P d'E.coli unit a la seqüència guia per l'extrem 3' (ribozim M1GS). Abans però de dirigir el ribozim, s'han estudiat l'estructura i la variabilitat d'una regió del genoma del virus ja que s'ha descrit que són factors que poden limitar l'eficiència de qualsevol ribozim. Derivat d'aquests estudis s'aporten dades sobre accessibilitat i variabilitat d'una regió interna del genoma del virus de l'hepatitis C, la zona d'unió de la regió E2/NS2 (regió 2658-2869). L'estudi d'accessibilitat revela que la regió 2658-2869 del genoma del virus conté dominis oberts i tancats i que la transició entre uns i altres no és brusca si es compara amb altres regions d'estructura coneguda (regió 5' no codificant). Els resultats dels assajos in vitro amb els dos models de RNasa P mostren que s'ha aconseguit dirigir tant la ribonucleasa P humana com el ribozim M1GS cap a una zona, predeterminada segons l'estudi d'accessibilitat, com a poc estructurada i tallar l'RNA del virus. De l'anàlisi de mutacions, però, es dedueix que la regió estudiada és variable. Tot i dirigir el ribozim cap a la zona més accessible, la variació de la diana podria afectar la interacció amb la seqüència guia i per tant disminuir l'eficiència de tall. Si es proposés una estratègia terapèutica consistiria en un atac simultani de vàries dianes.D'altra banda i derivat d'un resultat inesperat on s'ha observat en els experiments control que l'extracte de RNasa P humana tallava l'RNA viral en absència de seqüències guia externes, s'ha caracteritzat una nova interacció entre l'RNA del VHC i la RNasa P humana. Per a la identificació de l'enzim responsable dels talls s'han aplicat diferents tècniques que es poden dividir en mètodes directes (RNA fingerprinting) i indirectes (immunoprecipitació i inhibicions competitives). Els resultats demostren que la ribonucleasa P humana, i no un altre enzim contaminant de l'extracte purificat, és la responsable dels dos talls específics observats i que es localitzen, un a l'entrada interna al ribosoma (IRES) i molt a prop del codó AUG d'inici de la traducció i l'altre entre la regió codificant estructural i no estructural. La ribonucleasa P és un dels enzims del metabolisme del tRNA que s'utilitza per identificar estructures similars al tRNA en substrats diferents del substrat natural. Així doncs, el fet que la ribonucleasa P reconegui i talli el genoma del VHC en dues posicions determinades suggereix que, a les zones de tall, el virus conté estructures semblants al substrat natural, és a dir estructures tipus tRNA. A més, tot i que el VHC és molt variable, els resultats indiquen que aquestes estructures poden ser importants per el virus, ja que es mantenen en totes les variants naturals analitzades. Creiem que la seva presència podria permetre al genoma interaccionar amb factors cel·lulars que intervenen en la biologia del tRNA,particularment en el cas de l'estructura tipus tRNA que es localitza a l'element IRES. Independentment però de la seva funció, es converteixen en unes noves dianes terapèutiques per a la RNasa P. S'ha de replantejar però l'estratègia inicial ja que la similitud amb el tRNA les fa susceptibles a l'atac de la ribonucleasa P, directament, en absència de seqüències guia externes.
Hepatitis C virus is a human pathogen causing chronic liver disease in 170 million people worldwide. The virus is classified within the family Flaviviridae. The RNA genome is single-stranded and functions as the sole mRNA species for translation. It comprises a 5'-untranslated region, which functions as an internal ribosome entry site, and a long open reading frame, which encodes a polyprotein precursor of about 3010 amino acids, that is cleaved into structural (core, envelope 1, envelope 2 and p7) and non-structural (NS-2, NS-3, NS-4 and NS-5) proteins; followed by a 3' non-coding region. Analyzing significant numbers of cDNA clones of hepatitis C virus (HCV) from single isolates provides unquestionable proof that the viral genome cannot be defined by a single sequence, but rather by a population of variant sequences closely related to one another. In the infected patient, a master (the most frequently represented sequence) and a spectrum of mutant sequences may be isolated at any given time during chronic infection. This manner of organizing genetic information, which characterizes most RNA viruses, is referred to as quasispecies. HCV resistance to treatment (either alone or in combination with ribavirin) is one of the most important clinical implications predicted by the quasispecies model suggesting the necessity to seek new therapies. HCV therapeutic strategies based on ribozyme cleavage are leading candidates. The ribozyme activity of Ribonuclease P (RNase P) is among proposed antiviral agents. RNase P is a ubiquitous cellular endonuclease and one of the most abundant and efficient enzymes in the cell. This enzyme is a ribonucleoprotein complex that catalyzes a hydrolysis reaction to remove the leader sequence of precursor tRNA to generate the mature tRNA. Substrate recognition by the RNase P ribozyme does not rely on sequence requirements but on structural features of the RNA substrate. Custom-designed ribo-oligonucleotides, which hybridize with the target, called external guide sequences (EGSs), may provide the RNA structure which RNase P recognizes and cleaves in the hybridized complex. Recognition of structures instead of sequences may represent a great advantage in the fight against variable viruses because single or even double mutations in the target may be tolerated for RNase P recognition.
One of the major aims of this work is to cleave HCV RNA using the RNase P ribozyme guided by EGS. To expand investigation of targeting in the HCV genome we assessed accessibility and low potential of variation of the target RNA since it is described that are crucial requirements for ribozyme therapy against viral infections. In the hepatitis C virus, the sequence of the 5' non coding region is conserved but the highly folded RNA structure severely limits the number of accessible sites. We have considered an internal genomic region whose sequence variation has been widely investigated. We have first mapped the accessibility of the genomic RNA to complementary DNAs within an internal genomic region. We performed a kinetic and thermodynamic study. Accordingly, we have designed and assayed four RNase P ribozymes targeted to the selected sites. Considerations on RNA structural accessibility and sequence variation indicate that several target sites should be defined for simultaneous attack. While performing targeting experiments on HCV RNA transcripts with RNase P we have found that, surprisingly, purified RNase P (peak activity) from HeLa cells cleaved HCV genomic RNA efficiently at two sites in the absence of EGSs. We report the techniques used to prove that the cleavage is specific to human RNase P (indirect methods: immunoprecipitation and competitive inhibition), and to show where cleavage occurs (direct method: RNA fingerprinting). We have confirmed that human RNase P is responsible for HCV RNA processing and that the two cleavages sites are in the IRES HCV domain, close to AUG initiator triplet, and in the E2/NS2 junction fragment (between structural and non structural coding region). To define cleavage by RNase P as a general property of HCV, viral sequences obtained from different patients were compared for RNase P cleavage accessibility. Cleavage was consistently observed in all sequences tested although with different efficiencies. Since RNase P recognizes and cleaves tRNA-like structures, we believe that such recognition by RNase P is an indication for the presence of two possible tRNA-like structures in the HCV genome. Comparison of such results at the two HCV RNase P cleavage sites should help us to understand in greater detail HCV substrate structure, tRNA mimicry, rules underlying recognition by human RNase P, and, in the particular case of the IRES motif, possible participation in translation. Whatever the role of such tRNA-like structures, such a strong tendency to maintain them might be important in the development of therapeutic strategies against the virus because they can represent highly susceptible targets for RNase P.
Freyhult, Eva. "A Study in RNA Bioinformatics : Identification, Prediction and Analysis." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8305.
Повний текст джерелаPrévost, Gilles. "Essais de clonage du gene de l'arginyl-arnt synthetase de saccharomyces cerevisiae : determination des domaines fonctionnels de l'aspartyl-arnt synthetase de saccharomyces cerevisiae." Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13015.
Повний текст джерелаComandur, Roopa. "Structure of Retroviral 5′-Untranslated Regions and Interactions with Host and Viral Proteins." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu148060178765983.
Повний текст джерелаMarechal, Laurence. "Contribution a l'etude des trna mitochondriaux et de leurs genes, chez les plantes superieures." Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13019.
Повний текст джерелаChristopher, David Alan. "Structure and expression of a Euglena gracilis chloroplast transcription unit encoding 11 ribosomal protein genes, a tRNA gene and a 2.8 kb intergenic region." Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184937.
Повний текст джерелаCavarelli, Jean. "Etude cristallographique d'un complexe nucleoproteique forme entre l'aspartyl-trna synthetase de levure et l'acide ribonucleique de transfert specifique de l'acide aspartique." Strasbourg 1, 1987. http://www.theses.fr/1987STR13160.
Повний текст джерелаThomas, Sherine Elizabeth. "Targeting Mycobacterium abscessus infection in cystic fibrosis : a structure-guided fragment-based drug discovery approach." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289126.
Повний текст джерелаMuchenditsi, Abigael M. "Effects of Metal Ions and Loop Stability on the Structure and Function of the T Box Antiterminator RNA and its complex with Model tRNA." Ohio University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1251219465.
Повний текст джерелаFLORENTZ, EGELE CATHERINE. "L'extremite 3'oh aminoacyable du rna du virus de la mosaique jaune du navet : relations entre structure et fonctions." Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13181.
Повний текст джерелаGuelorget, Amandine. "Etude de la structure et de la région-spécificité de la m1A57/58 méthyltransférase d'ARNt de l'archée Pyrococcus abyssi." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00612159.
Повний текст джерелаSANGARE, ABDOURAHAMANE. "Etude de la structure des genes de trna de la mitochondrie du mais (zea mays) et comparaison de leur organisation dans les lignees male-fertile (n) et male-sterile (cms-t)." Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR13163.
Повний текст джерелаCastagné, Claire. "Analyse par résonance magnétique nucléaire des interactions ADN-protéine : étude des facteurs de transcription Rev-erb [bêta] et SRY ; détermination de la structure secondaire du domaine C-terminal de la tyrosyl'RNA synthétase." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE10039.
Повний текст джерелаQuivy, Jean-Pierre. "La tyrosyl-tRNA synthétase de germe de blé : purification et caractérisation ; étude de son effet sur la traduction in vitro du RNA du virus de la mosai͏̈que du brome, recherche de son gène." Grenoble 1, 1991. http://www.theses.fr/1991GRE10108.
Повний текст джерелаPettersson, B. M. Fredrik. "tRNA Gene Structures in Bacteria." Doctoral thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-100439.
Повний текст джерелаPIERRAT, STURCHLER CHRISTINE. "Etude structurale et fonctionnelle du trna selenocysteine eucaryote." Université Louis Pasteur (Strasbourg) (1971-2008), 1994. http://www.theses.fr/1994STR13209.
Повний текст джерелаTorres, Larios Alfredo. "Structural studies on threonyl and glycyl tRNA synthetases." Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13072.
Повний текст джерелаThe analysis of different complexed states on the system of ThrRS shows that the binding of the amino acid promotes a movement in the Ca position of 50 amino acids in one side of the catalytic domain. The binding of ATP triggers a movement in the Ca position of a salt bridge-locked region that is part of the core b-sheet cradling the small substrates. Two other small regions that surround the catalytic site move due to the small substrate binding in a cooperative way. The tRNA interacts with all four of these loops and several residues initially bound to threonine or ATP switch to a position in which they can contact the tRNA. The crystal structures of S. Aureus ThrRS and of the N-terminal region of E. Coli ThrRS show the presence of one metal ion and of a putative serine in the editing site, respectively. The role of the metal ion and the exact orientation of the amino acid could not be determined unambiguously, suggesting the low affinity of the sites. E. Coli ThrRS represses its own translation by binding to an operator located upstream of the initiation codon. The crystal structure of the complex between the core of ThrRS and the essential domain of the operator shows that the recognition mode of the tRNA anticodon loop has been utilized by the mRNA to initiate the binding. The final position of the operator, upon which the control mechanism is based, relies on a characteristic RNA motif adapted to the enzyme surface. The crystal structure of the a-subunit of E. Coli GlyRS shows that this protein forms most of the canonic catalytic core of the class II tRNA synthetases. This subunit shows unambiguously the presence of motif 1 and 2, difficult to infer at the sequence level. The structure differs from the core of other class II aaRS by the presence of three helices covering 80 residues of the C-terminal region and situated on top of the antiparallel b strand. The quaternary structure of this enzyme would be a2b2, in contrast with the (ab)2 case presented in PheRS
Bou, Nader Charles. "Structural and Functional characterization of flavoenzymes involved in posttranscriptional modification of tRNA." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066205/document.
Повний текст джерелаPosttranscriptional modification of ribonucleic acids (RNAs) is a crucial maturation step conserved in all domains of life. During my thesis, I have brought structural and functional insights on flavoenzymes involved in transfer RNA (tRNA) modifications: dihydrouridine synthase (Dus) responsible for dihydrouridine formation using flavin mononucleotide (FMN) and TrmFO responsible for C5 methylation of uridine position 54 relying on flavin adenosine dinucleotide (FAD) and methylenetetrahydrofolate. To elucidate the chemical mechanism of TrmFO we designed an apoprotein via a single mutation that could be reconstituted in vitro with FAD. Furthermore, we chemically synthesized the postulated intermediate active species consisting of a flavin iminium harboring a methylene moiety on the isoalloxazine N5 that was further characterized by mass spectrometry and UV-visible spectroscopy. Reconstitution of TrmFO with this molecule restored in vitro activity on a tRNA transcript proving that TrmFO uses FAD as a methylating agent via a reductive methylation.Dus2 reduces U20 and is comprised of a canonical Dus domain however, mammals have an additional double-stranded RNA-binding domain (dsRBD). To bring functional insight for this modular organization, we showed that only full length human Dus2 was active while its isolated domains were not. tRNA recognition is driven by the dsRBD via binding the acceptor and TΨ stem of tRNA with higher affinity then dsRNA as evidenced by NMR. We further solved the X-ray structures for both domains showing redistribution of surface positive charges justifying the involvement of this dsRBD for tRNA recognition in mammalian Dus2. This was attributed to a peculiar N-terminal extension proven by mutational analysis and an X-ray structure of dsRBD in complex with 22-nucleotide dsRNA. Altogether our work illustrates how during evolution, Dus2 enzymes acquired an engineered dsRBD for efficient tRNA binding via a ruler mechanism
García, Lema Jorge. "Structural studies on human adenosine-to-inosine tRNA editing." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/671423.
Повний текст джерелаPoterszman, Arnaud. "Etude structurale de l'aspartyl-trna synthetase de thermus thermophilus." Université Louis Pasteur (Strasbourg) (1971-2008), 1993. http://www.theses.fr/1993STR13196.
Повний текст джерела