Relevant bibliographies by topics / IRES – Internal Ribosome Entry Site

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Academic literature on the topic 'IRES – Internal Ribosome Entry Site'

Author: Grafiati
Published: 4 June 2021
Last updated: 12 February 2022

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Journal articles on the topic "IRES – Internal Ribosome Entry Site"

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Au, Hilda H., Gabriel Cornilescu, Kathryn D. Mouzakis, Qian Ren, Jordan E. Burke, Seonghoon Lee, Samuel E. Butcher, and Eric Jan. "Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection." Proceedings of the National Academy of Sciences 112, no. 47 (November 9, 2015): E6446—E6455. http://dx.doi.org/10.1073/pnas.1512088112.

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The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit the ribosome and initiate translation at a non-AUG codon. A subset of dicistrovirus IRESs directs translation in the 0 and +1 frames to produce the viral structural proteins and a +1 overlapping open reading frame called ORFx, respectively. Here we show that specific mutations of two unpaired adenosines located at the core of the three-helical junction of the honey bee dicistrovirusIsraeli acute paralysis virus(IAPV) IRES PKI domain can uncouple 0 and +1 frame translation, suggesting that the structure adopts distinct conformations that contribute to 0 or +1 frame translation. Using a reconstituted translation system, we show that ribosomes assembled on mutant IRESs that direct exclusive 0 or +1 frame translation lack reading frame fidelity. Finally, a nuclear magnetic resonance/small-angle X-ray scattering hybrid approach reveals that the PKI domain of the IAPV IRES adopts an RNA structure that resembles a complete tRNA. The tRNA shape-mimicry enables the viral IRES to gain access to the ribosome tRNA-binding sites and form intermolecular contacts with the ribosome that are necessary for initiating IRES translation in a specific reading frame.
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Terenin, Ilya M., Sergei E. Dmitriev, Dmitri E. Andreev, Elizabeth Royall, Graham J. Belsham, Lisa O. Roberts, and Ivan N. Shatsky. "A Cross-Kingdom Internal Ribosome Entry Site Reveals a Simplified Mode of Internal Ribosome Entry." Molecular and Cellular Biology 25, no. 17 (September 1, 2005): 7879–88. http://dx.doi.org/10.1128/mcb.25.17.7879-7888.2005.

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ABSTRACT Rhopalosiphum padi virus (RhPV) is an insect virus of the Dicistroviridae family. Recently, the 579-nucleotide-long 5′ untranslated region (UTR) of RhPV has been shown to contain an internal ribosome entry site (IRES) that functions efficiently in mammalian, plant, and insect in vitro translation systems. Here, the mechanism of action of the RhPV IRES has been characterized by reconstitution of mammalian 48S initiation complexes on the IRES from purified components combined with the toeprint assay. There is an absolute requirement for the initiation factors eIF2 and eIF3 and the scanning factor eIF1 to form 48S complexes on the IRES. In addition, eIF1A, eIF4F (or the C-terminal fragment of eIF4G), and eIF4A strongly stimulated the assembly of this complex, whereas eIF4B had no effect. Although the eIF4-dependent pathway is dominant in the RhPV IRES-directed cell-free translation, omission of either eIF4G or eIF4A or both still allowed the assembly of 48S complexes from purified components with ∼23% of maximum efficiency. Deletions of up to 100 nucleotides throughout the 5′-UTR sequence produced at most a marginal effect on the IRES activity, suggesting the absence of specific binding sites for initiation factors. Only deletion of the U-rich unstructured 380-nucleotide region proximal to the initiation codon resulted in a complete loss of the IRES activity. We suggest that the single-stranded nature of the RhPV IRES accounts for its strong but less selective potential to bind key mRNA recruiting components of the translation initiation apparatus from diverse origins.
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Beales, Lucy P., Andreas Holzenburg, and David J. Rowlands. "Viral Internal Ribosome Entry Site Structures Segregate into Two Distinct Morphologies." Journal of Virology 77, no. 11 (June 1, 2003): 6574–79. http://dx.doi.org/10.1128/jvi.77.11.6574-6579.2003.

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ABSTRACT An increasing number of viruses have been shown to initiate protein synthesis by a cap-independent mechanism involving internal ribosome entry sites (IRESs). Predictions of the folding patterns of these RNA motifs have been based primarily on sequence and biochemical analyses. Biophysical confirmation of the models has been achieved only for the IRES of hepatitis C virus (HCV), which adopts an open structure consisting of two major stems. We have conducted an extensive comparison of flavivirus and picornavirus IRES elements by negative stain transmission electron microscopy. All of the flavivirus IRESs we examined (those of GB virus-B, GB virus-C, and classical swine fever virus) fold to give a structure similar to that of the HCV IRES, as does an IRES recently found on mRNA encoded by human herpesvirus 8. The larger picornavirus IRESs (those of foot-and-mouth disease virus, rhinovirus, encephalomyocarditis virus, and hepatitis A virus) are morphologically similar, comprising a backbone with two protruding stems, and distinct from the flavivirus IRESs.
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Ochs, Kerstin, Lanja Saleh, Gergis Bassili, Volker H. Sonntag, Amandus Zeller, and Michael Niepmann. "Interaction of Translation Initiation Factor eIF4B with the Poliovirus Internal Ribosome Entry Site." Journal of Virology 76, no. 5 (March 1, 2002): 2113–22. http://dx.doi.org/10.1128/jvi.76.5.2113-2122.2002.

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ABSTRACT Poliovirus translation is initiated at the internal ribosome entry site (IRES). Most likely involving the action of standard initiation factors, this highly structured cis element in the 5" noncoding region of the viral RNA guides the ribosome to an internal silent AUG. The actual start codon for viral protein synthesis further downstream is then reached by ribosomal scanning. In this study we show that two of the secondary structure elements of the poliovirus IRES, domain V and, to a minor extent, domain VI, are the determinants for binding of the eukaryotic initiation factor eIF4B. Several mutations in domain V which are known to greatly affect poliovirus growth also seriously impair the binding of eIF4B. The interaction of eIF4B with the IRES is not dependent on the presence of the polypyrimidine tract-binding protein, which also binds to the poliovirus IRES. In contrast to its weak interaction with cellular mRNAs, eIF4B remains tightly associated with the poliovirus IRES during the formation of complete 80S ribosomes. Binding of eIF4B to the IRES is energy dependent, and binding of the small ribosomal subunit to the IRES requires the previous energy-dependent association of initiation factors with the IRES. These results indicate that the interaction of eIF4B with the 3" region of the poliovirus IRES may be directly involved in translation initiation.
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Oumard, A., M. Hennecke, H. Hauser, and M. Nourbakhsh. "Translation of NRF mRNA Is Mediated by Highly Efficient Internal Ribosome Entry." Molecular and Cellular Biology 20, no. 8 (April 15, 2000): 2755–59. http://dx.doi.org/10.1128/mcb.20.8.2755-2759.2000.

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ABSTRACT The ubiquitous transcription factor NRF (NF-κB repressing factor) is a constitutive transcriptional silencer of the multifunctional cytokine interferon-β. NRF mRNA contains a long 5′ untranslated region (5′UTR) predicted to fold into a strong secondary structure. The presence of stable hairpins is known to be incompatible with efficient translation by ribosomal scanning. Using dicistronic reporter gene constructs, we show that the NRF 5′UTR acts as an internal ribosome entry site (IRES) which directs ribosomes to the downstream start codon by a cap-independent mechanism. The relative activity of this IRES in various cell lines is at least 30-fold higher than that of picornaviral IRESs. The NRF 5′UTR also functions as a translational enhancer in the context of monocistronic mRNAs. Our results indicate that the NRF 5′UTR contains a highly potent IRES, which may allow for an alternate mode of translation under physiological conditions in which cap-dependent translation is inhibited.
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Spriggs, Keith A., Laura C. Cobbold, Catherine L. Jopling, Rebecca E. Cooper, Lindsay A. Wilson, Mark Stoneley, Mark J. Coldwell, et al. "Canonical Initiation Factor Requirements of the Myc Family of Internal Ribosome Entry Segments." Molecular and Cellular Biology 29, no. 6 (January 5, 2009): 1565–74. http://dx.doi.org/10.1128/mcb.01283-08.

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ABSTRACT Initiation of protein synthesis in eukaryotes requires recruitment of the ribosome to the mRNA and its translocation to the start codon. There are at least two distinct mechanisms by which this process can be achieved; the ribosome can be recruited either to the cap structure at the 5′ end of the message or to an internal ribosome entry segment (IRES), a complex RNA structural element located in the 5′ untranslated region (5′-UTR) of the mRNA. However, it is not well understood how cellular IRESs function to recruit the ribosome or how the 40S ribosomal subunits translocate from the initial recruitment site on the mRNA to the AUG initiation codon. We have investigated the canonical factors that are required by the IRESs found in the 5′-UTRs of c-, L-, and N-myc, using specific inhibitors and a tissue culture-based assay system, and have shown that they differ considerably in their requirements. The L-myc IRES requires the eIF4F complex and the association of PABP and eIF3 with eIF4G for activity. The minimum requirements of the N- and c-myc IRESs are the C-terminal domain of eIF4G to which eIF4A is bound and eIF3, although interestingly this protein does not appear to be recruited to the IRES RNA via eIF4G. Finally, our data show that all three IRESs require a ternary complex, although in contrast to c- and L-myc IRESs, the N-myc IRES has a lesser requirement for a ternary complex.
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Ochs, Kerstin, RenéC Rust, and Michael Niepmann. "Translation Initiation Factor eIF4B Interacts with a Picornavirus Internal Ribosome Entry Site in both 48S and 80S Initiation Complexes Independently of Initiator AUG Location." Journal of Virology 73, no. 9 (September 1, 1999): 7505–14. http://dx.doi.org/10.1128/jvi.73.9.7505-7514.1999.

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ABSTRACT Most eukaryotic initiation factors (eIFs) are required for internal translation initiation at the internal ribosome entry site (IRES) of picornaviruses. eIF4B is incorporated into ribosomal 48S initiation complexes with the IRES RNA of foot-and-mouth disease virus (FMDV). In contrast to the weak interaction of eIF4B with capped cellular mRNAs and its release upon entry of the ribosomal 60S subunit, eIF4B remains tightly associated with the FMDV IRES during formation of complete 80S ribosomes. Binding of eIF4B to the IRES is energy dependent, and binding of the small ribosomal subunit to the IRES requires the previous energy-dependent association of initiation factors with the IRES. The interaction of eIF4B with the IRES in 48S and 80S complexes is independent of the location of the initiator AUG and thus independent of the mechanism by which the small ribosomal subunit is placed at the actual start codon, either by direct internal ribosomal entry or by scanning. eIF4B does not greatly rearrange its binding to the IRES upon entry of the ribosomal subunits, and the interaction of eIF4B with the IRES is independent of the polypyrimidine tract-binding protein, which enhances FMDV translation.
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Camerini, Valentina, Didier Decimo, Laurent Balvay, Mauro Pistello, Mauro Bendinelli, Jean-Luc Darlix, and Théophile Ohlmann. "A Dormant Internal Ribosome Entry Site Controls Translation of Feline Immunodeficiency Virus." Journal of Virology 82, no. 7 (January 30, 2008): 3574–83. http://dx.doi.org/10.1128/jvi.02038-07.

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ABSTRACT The characterization of internal ribosome entry sites (IRESs) in virtually all lentiviruses prompted us to investigate the mechanism used by the feline immunodeficiency virus (FIV) to produce viral proteins. Various in vitro translation assays with mono- and bicistronic constructs revealed that translation of the FIV genomic RNA occurred both by a cap-dependent mechanism and by weak internal entry of the ribosomes. This weak IRES activity was confirmed in feline cells expressing bicistronic RNAs containing the FIV 5′ untranslated region (UTR). Surprisingly, infection of feline cells with FIV, but not human immunodeficiency virus type 1, resulted in a great increase in FIV translation. Moreover, a change in the cellular physiological condition provoked by heat stress resulted in the specific stimulation of expression driven by the FIV 5′ UTR while cap-dependent initiation was severely repressed. These results reveal the presence of a “dormant” IRES that becomes activated by viral infection and cellular stress.
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Murray, Kenneth E., Benjamin P. Steil, Allan W. Roberts, and David J. Barton. "Replication of Poliovirus RNA with Complete Internal Ribosome Entry Site Deletions." Journal of Virology 78, no. 3 (February 1, 2004): 1393–402. http://dx.doi.org/10.1128/jvi.78.3.1393-1402.2004.

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ABSTRACT cis-acting RNA sequences and structures in the 5′ and 3′ nontranslated regions of poliovirus RNA interact with host translation machinery and viral replication proteins to coordinately regulate the sequential translation and replication of poliovirus RNA. The poliovirus internal ribosome entry site (IRES) in the 5′ nontranslated region (NTR) has been implicated as a cis-active RNA required for both viral mRNA translation and viral RNA replication. To evaluate the role of the IRES in poliovirus RNA replication, we exploited the advantages of cell-free translation-replication reactions and preinitiation RNA replication complexes. Genetic complementation with helper mRNAs allowed us to create preinitiation RNA replication complexes containing RNA templates with defined deletions in the viral open reading frame and the IRES. A series of deletions revealed that no RNA elements of either the viral open reading frame or the IRES were required in cis for negative-strand RNA synthesis. The IRES was dispensable for both negative- and positive-strand RNA syntheses. Intriguingly, although small viral RNAs lacking the IRES replicated efficiently, the replication of genome length viral RNAs was stimulated by the presence of the IRES. These results suggest that RNA replication is not directly dependent on a template RNA first functioning as an mRNA. These results further suggest that poliovirus RNA replication is not absolutely dependent on any protein-RNA interactions involving the IRES.
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Rijnbrand, René, Geoffrey Abell, and Stanley M. Lemon. "Mutational Analysis of the GB Virus B Internal Ribosome Entry Site." Journal of Virology 74, no. 2 (January 15, 2000): 773–83. http://dx.doi.org/10.1128/jvi.74.2.773-783.2000.

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ABSTRACT GB virus B (GBV-B) is a recently discovered hepatotropic flavivirus that is distantly related to hepatitis C virus (HCV). We show here that translation of its polyprotein is initiated by internal entry of ribosomes on GBV-B RNA. We analyzed the translational activity of dicistronic RNA transcripts containing wild-type or mutated 5′ nontranslated GBV-B RNA (5′NTR) segments, placed between the coding sequences of two reporter proteins, in vitro in rabbit reticulocyte lysate and in vivo in transfected BT7-H cells. We related these results to a previously proposed model of the secondary structure of the GBV-B 5′NTR (M. Honda, et al. RNA 2:955–968, 1996). We identified an internal ribosome entry site (IRES) bounded at its 5′ end by structural domain II, a location analogous to the 5′ limit of the IRES in both the HCV and pestivirus 5′NTRs. Mutational analysis confirmed the structure proposed for domain II of GBV-B RNA, and demonstrated that optimal IRES-mediated translation is dependent on each of the putative RNA hairpins in this domain, including two stem-loops not present in the HCV or pestivirus structures. IRES activity was also absolutely dependent on (i) phylogenetically conserved, adenosine-containing bulge loops in domain III and (ii) the primary nucleotide sequence of stem-loop IIIe. IRES-directed translation was inhibited by a series of point mutations predicted to stabilize stem-loop IV, which contains the initiator AUG codon in its loop segment. A reporter gene was translated most efficiently when fused directly to the initiator AUG codon, with no intervening downstream GBV-B sequence. This finding indicates that the 3′ limit of the GBV-B IRES is at the initiator AUG and that it does not require downstream polyprotein-coding sequence as suggested for the HCV IRES. These results show that the GBV-B IRES, while sharing a common general structure, differs both structurally and functionally from other flavivirus IRES elements.
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Dissertations / Theses on the topic "IRES – Internal Ribosome Entry Site"

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Hsieh, Fang-I. "Compartmentalisation of internal ribosome entry site (IRES) quasispecies of hepatitis C virus (HCV) and differences in polyprotein expression." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432063.

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Sadahiro, Akitoshi. "Translation of Hepatitis A Virus IRES Is Upregulated by a Hepatic Cell-Specific Factor." Kyoto University, 2019. http://hdl.handle.net/2433/242387.

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Zakari, Musinu. "The SMC loader Scc2 promotes ncRNA biogenesis and translational fidelity in Saccharomyces cerevisiae." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066148/document.

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Le complexe Scc2-Scc4 est essentiel pour l’association du complexe cohésine sur l’ADN. Les proteines Cohésine génèrent la cohésion entre les chromatides sœurs, ce qui est essentiel pour la ségrégation des chromosomes. Scc2 (également connu sous le nom NIPBL) est muté chez les patients atteints du syndrome de Cornelia de Lange, une maladie multi-organique caractérisée par des anomalies du développement du visage, de la developpement mental cardiaque et du tractus gastro-intestinal. Comment les mutations localisées au niveau du gène codant pour la proteine Scc2 conduisent à des anomalies du développement chez les patients n’a pas encore été élucidé. Une des hypothèses est que la liaison de Scc2 / cohésine à différentes régions du génome a une incidence sur la transcription. Chez la levure de bière, il a été montre que Scc2 se lie aux genes transcrits par l'ARN Pol III (les ARNt et spliceosomals) , ainsi qu‘aux gènes transcrits par l'ARN Pol II codant pour des petits ARN nucléolaires et nucléaires (snARN et snoARNs ) et des gènes de protéines ribosomiques. Nous rapportons ici que Scc2 est important pour l'expression de ces gènes. Scc2 et le régulateur transcriptionnel Paf1 collaborent pour promouvoir la production de Box H / ACA snoARNs qui guident la pseudouridylation des ARN y compris l'ARN ribosomal. Une mutation de Scc2 a été associée à des défauts dans la production d'ARN ribosomal, la biogenèse des ribosomes, et del’épissage. Alors que le mutant Scc2 n'a pas de défaut général de la synthèse protéique, il montre un déphasage accrue et une réduction de l’utilisation du site interne d'entrée ribosomale (IRES)/ coiffe-indépendante. Ces résultats suggèrent que Scc2 favorise normalement un programme d'expression génétique qui prend en charge la fidélité de la traduction. Nous émettons l'hypothèse que le dysfonctionnement de traduction peut contribuer au syndrome de Cornelia de Lange, qui est causé par des mutations dans Scc2
The Scc2-Scc4 complex is essential for loading the cohesin complex onto DNA. Cohesin generates cohesion between sister chromatids, which is critical for chromosome segregation. Scc2 (also known as NIPBL) is mutated in patients with Cornelia de Lange syndrome, a multi-organ disease characterized by developmental defects in head, limb, cognition, heart, and the gastrointestinal tract. How mutations in Scc2 lead to developmental defects in patients is yet to be elucidated. One hypothesis is that the binding of Scc2/cohesin to different regions of the genome will affect transcription. In budding yeast, Scc2 has been shown to bind to RNA Pol III transcribed genes (tRNAs, and spliceosomal), as well as RNA Pol II-transcribed genes encoding small nuclear and nucleolar RNAs (snRNAs and snoRNAs) and ribosomal protein genes. Here, we report that Scc2 is important for gene expression. Scc2 and the transcriptional regulator Paf1 collaborate to promote the production of Box H/ACA snoRNAs which guide pseudouridylation of RNAs including ribosomal RNA. Mutation of Scc2 was associated with defects in the production of ribosomal RNA, ribosome biogenesis, and splicing. While the scc2 mutant does not have a general defect in protein synthesis, it shows increased frameshifting and reduced internal ribosomal entry site (IRES) usage/cap-independent translation. These findings suggest Scc2 normally promotes a gene expression program that supports translational fidelity. We hypothesize that translational dysfunction may contribute to the human disorder Cornelia de Lange syndrome, which is caused by mutations in Scc2
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Boni, Sébastien. "Observation in vitro de la modulation de l'activité traductionnelle de l'IRES du virus de l'hépatite C par certains facteurs viraux et mise au point d'un système d'étude cellulaire de son activité via un vecteur lentiviral." Paris 6, 2006. http://www.theses.fr/2006PA066446.

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Le virus de l’hépatite C pose un grave problème de santé du fait de sa prévalence élevé (3%) dans la population mondiale. Il est l’agent viral responsable de la survenue d’hépatites chroniques évoluant progressivement vers une cirrhose et/ou un carcinome hépatocellulaire. Son génome est composé d’un ARN monocaténaire de polarité positive d’environ 9600 nucléotides, flanqué à ses deux extrémités des régions 5’ (5’NC) et 3’ (3’NC) non codantes. Sa traduction est initiée par l’entrée directe des ribosomes au niveau d’une séquence hautement structurée et complexe, localisée dans la région 5’NC : l’IRES (Internal Ribosome Entry Site). La conservation de cette région entre les différents génotypes et sous-types viraux et son rôle fondamental dans l’initiation de la traduction, première étape du cycle viral, font de l’IRES une cible thérapeutique considérable en l’absence d’un traitement efficace et d’un vaccin. Les mécanismes d’initiation de la traduction au niveau de cette structure sont relativement bien connus, cependant la modulation de son activité reste mal comprise et demeure un sujet de controverse. Nous avons mis en évidence, in vitro, à l’aide d’un système de gène rapporteur un rôle modulateur dose-dépendant de la protéine structurale de capside (C-VHC) ajoutée en trans, ainsi qu’un rôle activateur en cis de la région 3’NC sur l’activité de l’IRES. Afin d’étudier et de valider ces observations ex vivo, nous avons mis au point un système cellulaire d’expression basé sur l’emploi de vecteurs lentiviraux. Ces derniers expriment un transcrit bicistronique comportant l’IRES du VHC et ont permis de quantifier l’activité traductionnelle de l’IRES dans les conditions proches de celles de l’infection virale au sein de différentes lignées cellulaires, et de valider notre système d’étude en testant l’inhibition de l’IRES par des agents thérapeutiques utilisés dans le traitement contre l’infection par le VHC.
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Bradford, Seth Stephen. "The Design and Evaluation of Catalytic MetalloDrugs Targeting HCV IRES RNA: Demonstration of a New Therapeutic Approach." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1345132549.

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Brocard, Michèle. "Etude des facteurs cellulaires impliqués dans l’initiation de la traduction médiée par le signal d’entrée interne des ribosomes du virus de l’hépatite C." Paris 6, 2007. http://www.theses.fr/2007PA066401.

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Le Virus de l'Hépatite C (VHC) est un virus à génome ARN positif, membre de la famille des Flaviviridae, dont la traduction est guidée par un Site d'Entrée Interne du Ribosome (IRES) situé dans la région 5' non traduite du génome. Il est connu que l'initiation de la traduction médiée par l'IRES du VHC nécessite peu de facteurs classiques de la traduction et alors que de nombreux facteurs cellulaires sont capables d'interagir avec cet IRES, aucun n'a été reconnu capable d'une interaction fonctionnelle de type ITAF. Nous avons démontré d'une part dans ce travail que la protéine PTB n'était pas un cofacteur de ce mécanisme. D'autre part ce travail a abouti à l'idée qu'une activité ATP-dépendante non classique est nécessaire à la formation du complexe d'initiation sur l'IRES du VHC. Ce dernier résultat est particulièrement intéressant car pourrait conduire à la détermination d'une nouvelle cible thérapeutique anti-virale.
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Mengardi, Chloé. "Étude de l'effet des microARN sur l'initiation de la traduction dirigée par l'IRES du Virus de l'Hépatite C." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSEN001.

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Les microARN (miARN) sont de petits ARN non-codants qui contrôlent l’expression génique, en s’hybridant, le plus souvent, de manière imparfaite à des séquences spécifiques qui se trouvent généralement dans la région non traduite en 3' (3’UTR) de transcrits cibles. Les miARN guident sur l’ARN messager (ARNm) un complexe protéique appelé RNA-induced Silencing Complex (RISC), composé des protéines Argonaute et TNRC6, qui perturbe l’initiation de la traduction et provoque la déadénylation et la dégradation du transcrit. C'est l’interaction entre le RISC et le complexe de pré-initiation de la traduction 43S (composé de la petite sous-unité ribosomique 40S et des facteurs d’initiation associés) qui entraîne la répression traductionnelle de l’ARNm ciblé. Des résultats récents ont démontré que le RISC perturbe le balayage de la région non traduite en 5’ (5’UTR) par le ribosome, étape qui requiert la présence de 2 facteurs d’initiation qui sont eIF4F qui reconnaît et lie la coiffe ainsi que la protéine PABP, fixée le long de la queue poly(A). Toutefois, les miARN peuvent également induire la stimulation de la traduction des transcrits cibles dans les cellules quiescentes, dans un lysat d’embryons de drosophiles ou encore dans les ovocytes de Xénope. Le mécanisme moléculaire de stimulation de l’expression par les miARN est encore mal connu mais requiert l’absence de queue poly(A) en 3’ des ARN cible et de TNRC6 au sein du complexe RISC. Le Virus de l’Hépatite C (VHC) possède en 5’ de son ARNg un site d’entrée interne du ribosome (IRES) qui recrute la petite sous-unité ribosomique 40S, sans nécessiter la reconnaissance de la coiffe par eIF4F, ni la protéine PABP, ni le balayage de la 5’UTR par le ribosome. Ces caractéristiques singulières nous ont conduits à rechercher l'impact du complexe RISC fixé en 3’ de l’ARNm sur l’initiation de la traduction du VHC. Pour cela, nous avons utilisé des transcrits contenant l'IRES du VHC en 5' et des sites d’hybridation du miARN let-7 en 3’. Ces ARNm ont ensuite été transfectés dans des lignées cellulaires hépatocytaires, ou non. A notre grande surprise, nous avons observé que la fixation du miARN let-7 sur la région 3' du transcrit stimulait fortement l’expression dirigée par l’IRES de VHC. Toutefois, l’augmentation de l’expression n’est pas due à la stabilisation du transcrit mais bien à une hausse significative de la synthèse protéique indépendamment d’un quelconque effet de miR-122. En utilisant d’autres IRES dites 'HCV-like', nous avons pu confirmer ces résultats et démontrer que, l’ajout d’une queue poly(A) en 3’ du transcrit, capable de fixer la PABP, annule cet effet stimulateur suggérant que l’absence de cette protéine est nécessaire pour que le complexe RISC stimule la traduction du VHC
MicroRNAs (miRNAs) are small non coding RNAs which control gene expression by recognizing and hybridizing to a specific sequence generally located in the 3’UTR of targeted messenger RNA (mRNA). miRNAs serve as a guide for the RNA-Induced Silencing Complex (RISC) that is composed by, at least, the Argonaute proteins and TNRC6. Recent studies have suggested that translation inhibition occurs first and is then followed by deadenylation and degradation of the targeted transcript. The miRNA-induced inhibition of protein synthesis occurs at the level of translation initiation during the ribosomal scanning step and it requires the presence of both the initiation factor eIF4G and the poly(A) Binding Protein (PABP). In this process, the RISC interacts with both PABP and 43S pre-initiation complex (composed by initiation factors and ribosome) and it results in the disruption of linear scanning of the ribosome along the 5’ Untranslated Region (5’UTR). In some specific cases, the binding of miRNAs to their target sequences can upregulate translation initiation. This has notably been demonstrated in G0 quiescent cells, drosophila embryos and Xenopus oocytes. Although the molecular mechanism by which upregulation occurs remains to be precisely determined, it appears that the absence of a poly(A) tail and the lack of availability of the TNRC6 proteins are amongst the major determinants. In the particular case of the Hepatitis C Virus (HCV), the genomic RNA is uncapped and non polyadenylated and harbors an Internal Ribosome Entry Site (IRES) which directly binds to the ribosome with no need for cap-recognition, PABP binding and ribosome scanning. These peculiar features of the HCV IRES prompted us to investigate how viral translation can be regulated by the miRNA machinery. In order to do that, we have used a mRNA that contains the HCV IRES in 5’ and 4 let-7 binding sites in its 3’ extremity. To most of our surprise, we have observed a strong stimulation of the expression of the HCV IRES when the construct is bearing the let-7 sites. This effect is not due to any interference with the miR-122 binding sites although the magnitude of stimulation reached the same level. Our data show that it is the presence of the RISC on the 3' end of the transcript that can stimulate internal ribosome entry at the 5' end. By using other HCV-like IRESes, we could confirm these data and further showed that the absence of a poly(A) tail was an absolute requirement for the stimulation to occur. These effects are not due to an increase of mRNA stability and are rather exerted at the level of translation
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8

Lourenco, Sofia. "Etude de la modulation de la traduction du virus de l'hépatite C par des facteurs viraux en cis et en trans et développement de nouveaux outils via le système lentiviral." Paris 6, 2008. http://www.theses.fr/2008PA066333.

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Le virus de l’hépatite C (VHC) est actuellement responsable d’un problème de santé mondiale infectant environ 3% de la population. Le VHC possède une molécule d’ARN simple brin et de polarité positive ainsi que deux régions non codantes (NC) 5’ et 3’. La traduction virale a lieu via une séquence interne d’entrée des ribosomes (IRES) située dans la région 5’NC. L’objectif de ce travail de thèse a été de clarifier le rôle de facteurs viraux en cis (3’NC) et en trans (C, NS5A, NS5B) dans la régulation de l’activité traductionnelle de l’IRES. Nous avons utilisé un système double rapporteur ARN, ciblant ainsi la traduction. D’après l’activité relative de l’IRES mesurée (rapport RLuc/FLuc) différents points ont été observés : 1) la région 3’NC stimule fortement l’activité IRES en cis, ce qui dépend de la structure secondaire globale; 2) une modulation dose et génotype dépendante de la traduction a été démontrée en présence de C et NS5B ; 3) aucun effet synergique n’a été observé entre les protéines virales ou entre les différents facteurs viraux. D’après ces résultats, les facteurs viraux étudiés agiraient de façon séquentielle pour moduler la traduction virale. Nous nous sommes ensuite focalisés sur le développement de nouveaux outils. Nous avons établi un système lentiviral bicistronique, qui s’est révélé efficace pour le criblage de drogues. Les expériences actuellement en cours visent l’établissement d’une lignée exprimant constitutivement l’ARN polymérase du phage T7 (T7 RNAp), permettant à la fois une analyse fine de la fonctionnalité de l’IRES, le criblage de drogues ainsi que l’étude d’autres virus, remplaçant le système vaccine couramment utilisé
Hepatitis C virus (HCV) is responsible of a major health problem, infecting 3% of world population. Hepatitis C Virus (HCV) possesses a positive single-stranded RNA genome with highly structured non coding (NC) regions at its extremities: 5’NC and 3’NC. Translation initiation of HCV RNA occurs via an Internal Ribosome Entry Site (IRES) located at its 5’end. Our aim was to clarify the role of cis (3’NCR) and trans (C, NS5A, NS5B) viral factors on the regulation of IRES activity. By the use of a dual RNA reporter system, targeting the translation step and avoiding the cryptic IRES promoter activity, relative IRES activities measured in luminometry (= RLuc/FLuc activities ratio) revealed the following features : 1) all the HCV 3’ non coding (NC) sequences tested highly stimulate in cis the IRES efficiency; 2) a dose and genotype dependent modulation of the translation in trans was shown with the capsid and NS5B ; and 3) not any cooperative effect could be obtained either between viral proteins, or in the presence of both cis and trans factors. Taking together these results encouraged us to propose a model in which the viral factors tested act sequentially to modulate viral translation and the switch to replication. We then focus on the development of novel tools for evaluating the IRES activity analysis. We established a bicistronic lentiviral system, which revealed efficient for drugs screening, however not adequate for a precise IRES activity analysis. Experiments actually in progress aim the precise analysis of IRES activity, drugs screening and in addition the study of other viruses, replacing the vaccine system currently used
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9

Jang, Christopher. "Characterization of the Dicistroviridae intergenic region internal ribosome entry site." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/35330.

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The IRES found in the intergenic (IGR) region of viruses belonging to the Dicistroviridae family is remarkable for its ability to bind directly to the ribosome with high affinity and initiate translation without the requirement for any initiation factors by mimicking a P/E hybrid tRNA. Here, we have conducted an in-depth biochemical characterization of the CrPV IGR IRES. We have found that the L1.1 region of the IRES is responsible for 80S assembly and reading frame maintenance, and may play an additional role downstream of ribosome binding. Additional studies on the modularity of the IRES showed that the two domains of the IGR IRES work independently, but in concert with one another to manipulate the ribosome. We then addressed the question of how the IGR IRES recruits ribosomes during periods of cellular stress, when inactive 80S couples accumulate in the cell. Here, we found that the IRES is able to bind directly to eEF2-associated 80S couples, providing a rationale as to how the IRES remains translated during these periods. Finally, we developed a new in vitro translation system to assess the functionality of specialized ribosomes, and used this system and the IGR IRES in order to ask questions about the pathology of dyskeratosis congenita. Though divergent from other viral IRESs, the simplicity of this tRNA-like IRES serves as a powerful model for understanding IRES functions in general, the role of tRNA/ribosome interactions that occur normally during translation, and how these processes are linked to the greater context of the cell.
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10

Green, Russell James. "Structural studies of the hepatitis C virus internal ribosome entry site." Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400961.

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Book chapters on the topic "IRES – Internal Ribosome Entry Site"

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Mehrtens, Sarah, and Marc R. Reboll. "Mapping of Internal Ribosome Entry Sites (IRES)." In RNA Mapping, 179–85. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1062-5_15.

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Valášek, Leoš Shivaya. "Internal Ribosome Entry Site, Eukaryotic." In Encyclopedia of Systems Biology, 1047–52. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-9863-7_824.

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Ehrenfeld, E., and B. L. Semler. "Anatomy of the Poliovirus Internal Ribosome Entry Site." In Current Topics in Microbiology and Immunology, 65–83. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79663-0_3.

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Rijnbrand, R. C. A., and S. M. Lemon. "Internal Ribosome Entry Site-Mediated Translation in Hepatitis C Virus Replication." In Current Topics in Microbiology and Immunology, 85–116. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-642-59605-6_5.

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Wang, C., and A. Siddiqui. "Structure and Function of the Hepatitis C Virus Internal Ribosome Entry Site." In Current Topics in Microbiology and Immunology, 99–115. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79663-0_5.

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Ehrenfeld, Ellie, and Natalya L. Teterina. "Initiation of Translation of Picornavirus RNAs: Structure and Function of the Internal Ribosome Entry Site." In Molecular Biology of Picornavirus, 157–69. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555817916.ch14.

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Kettinen, H., K. Grace, S. Grunert, B. Clarke, D. Rowlands, and R. Jackson. "Mapping of the Internal Ribosome Entry Site at the 5′ End of the Hepatitis C Virus Genome." In Viral Hepatitis and Liver Disease, 125–31. Tokyo: Springer Japan, 1994. http://dx.doi.org/10.1007/978-4-431-68255-4_34.

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Dibrov, Sergey M., and Thomas Hermann. "Structure of the HCV Internal Ribosome Entry Site Subdomain IIa RNA in Complex with a Viral Translation Inhibitor." In Methods in Molecular Biology, 329–35. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-2763-0_21.

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"IRES (internal ribosome entry site, also called RLP)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 1033–34. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_8746.

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Sonenberg, N., Y. Svitkin, and N. Siddiqui. "Internal Ribosome Entry Site-Mediated Translation." In Encyclopedia of Cell Biology, 307–16. Elsevier, 2016. http://dx.doi.org/10.1016/b978-0-12-394447-4.30042-6.

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Conference papers on the topic "IRES – Internal Ribosome Entry Site"

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Zong, Yu, Yulin Li, Xiaofei Liu, and Mark Daniel Pegram. "Abstract A65: Dicistronic reporter screen for Internal Ribosome Entry Site (IRES)-mediated translational regulation of truncated p110 ERBB2 isoform." In Abstracts: AACR Special Conference: Advances in Breast Cancer Research; October 7-10, 2017; Hollywood, CA. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1557-3125.advbc17-a65.

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Zong, Y., Y. Li, X. Liu, and MD Pegram. "Abstract P6-05-05: Discistronic reporter screen for internal ribosome entry site (IRES) - mediated translational regulation of truncated p110 ERBB2 isoform." In Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, Texas. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.sabcs17-p6-05-05.

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