La Banque centrale européenne et la nouvelle gouvernance économique européenne: le défi de l’intégration différenciée = The European Central Bank and the new European economic governance: the challenge of differential integration. Research Paper in Law 01/2015

No abstract

The 5S rRNA maturase, ribonuclease M5, is a Toprim domain family member

The maturation of 5S ribosomal RNA in low G+C Gram-positive bacteria is catalyzed by a highly conserved, ∼190 residue, enzyme, called ribonuclease M5 (RNase M5). Sequence alignment had predicted that the N-terminal half of RNase M5 would consist of a Toprim domain, a protein fold found in type IA and type II topoisomerases, DnaG-like primases, OLD family nucleases and RecR proteins [L. Aravind, D. D. Leipe and E. V. Koonin (1998) Nucleic Acids Res., 26, 4205–4213]. Here, we present structural modelling data and a mutational analysis of RNase M5 that confirms this hypothesis. The N-terminal half of RNase M5 can be fitted to the Toprim domain of the DnaG catalytic core. Mutation of amino acid residues highly conserved among RNase M5 enzymes and members of the Toprim domain family showed that alteration of residues critical for topoisomerase and primase activity also had a dramatic effect on the cleavage of 5S rRNA precursor by RNase M5 both in vivo and in vitro. This suggests that the mechanisms of double-stranded RNA cleavage by RNase M5 and double-stranded DNA cleavage by members of the topoisomerase family are related

Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

International audienceAbstract The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion

SrmB, a DEAD-box helicase involved in Escherichia coli ribosome assembly, is specifically targeted to 23S rRNA in vivo

DEAD-box proteins play specific roles in remodeling RNA or ribonucleoprotein complexes. Yet, in vitro, they generally behave as nonspecific RNA-dependent ATPases, raising the question of what determines their specificity in vivo. SrmB, one of the five Escherichia coli DEAD-box proteins, participates in the assembly of the large ribosomal subunit. Moreover, when overexpressed, it compensates for a mutation in L24, the ribosomal protein (r-protein) thought to initiate assembly. Here, using the tandem affinity purification (TAP) procedure, we show that SrmB forms a complex with r-proteins L4, L24 and a region near the 5′-end of 23S rRNA that binds these proteins. In vitro reconstitution experiments show that the stability of this complex reflects cooperative interactions of SrmB with L4, L24 and rRNA. These observations are consistent with an early role of SrmB in assembly and explain the genetic link between SrmB and L24. Besides its catalytic core, SrmB possesses a nonconserved C-terminal extension that, we show, is not essential for SrmB function and specificity. In this regard, SrmB differs from DbpA, another DEAD-box protein involved in ribosome assembly

The Role of Disordered Ribosomal Protein Extensions in the Early Steps of Eubacterial 50 S Ribosomal Subunit Assembly

Although during the past decade research has shown the functional importance of disorder in proteins, many of the structural and dynamics properties of intrinsically unstructured proteins (IUPs) remain to be elucidated. This review is focused on the role of the extensions of the ribosomal proteins in the early steps of the assembly of the eubacterial 50 S subunit. The recent crystallographic structures of the ribosomal particles have revealed the picture of a complex assembly pathway that condenses the rRNA and the ribosomal proteins into active ribosomes. However, little is know about the molecular mechanisms of this process. It is thought that the long basic r-protein extensions that penetrate deeply into the subunit cores play a key role through disorder-order transitions and/or co-folding mechanisms. A current view is that such structural transitions may facilitate the proper rRNA folding. In this paper, the structures of the proteins L3, L4, L13, L20, L22 and L24 that have been experimentally found to be essential for the first steps of ribosome assembly have been compared. On the basis of their structural and dynamics properties, three categories of extensions have been identified. Each of them seems to play a distinct function. Among them, only the coil-helix transition that occurs in a phylogenetically conserved cluster of basic residues of the L20 extension appears to be strictly required for the large subunit assembly in eubacteria. The role of α helix-coil transitions in 23 S RNA folding is discussed in the light of the calcium binding protein calmodulin that shares many structural and dynamics properties with L20

The skeleton of the staghorn coral Acropora millepora: molecular and structural characterization

15 pagesInternational audienceThe scleractinian coral Acropora millepora is one of the most studied species from the Great Barrier Reef. This species has been used to understand evolutionary, immune and developmental processes in cnidarians. It has also been subject of several ecological studies in order to elucidate reef responses to environmental changes such as temperature rise and ocean acidification (OA). In these contexts, several nucleic acid resources were made available. When combined to a recent proteomic analysis of the coral skeletal organic matrix (SOM), they enabled the identification of several skeletal matrix proteins, making A. millepora into an emerging model for biomineralization studies. Here we describe the skeletal microstructure of A. millepora skeleton, together with a functional and biochemical characterization of its occluded SOM that focuses on the protein and saccharidic moieties. The skeletal matrix proteins show a large range of isoelectric points, compositional patterns and signatures. Besides secreted proteins, there are a significant number of proteins with membrane attachment sites such as transmembrane domains and GPI anchors as well as proteins with integrin binding sites. These features show that the skeletal proteins must have strong adhesion properties in order to function in the calcifying space. Moreover this data suggest a molecular connection between the calcifying epithelium and the skeletal tissue during biocalcification. In terms of sugar moieties, the enrichment of the SOM in arabinose is striking, and the monosaccharide composition exhibits the same signature as that of mucus of acroporid corals. Finally, we observe that the interaction of the acetic acid soluble SOM on the morphology of in vitro grown CaCO3 crystals is very pronounced when compared with the calcifying matrices of some mollusks. In light of these results, we wish to commend Acropora millepora as a model for biocalcification studies in scleractinians, from molecular and structural viewpoints

An RNA-Binding Protein Secreted by a Bacterial Pathogen Modulates RIG-I Signaling.

RNA-binding proteins (RBPs) perform key cellular activities by controlling the function of bound RNAs. The widely held assumption that RBPs are strictly intracellular has been challenged by the discovery of secreted RBPs. However, extracellular RBPs have been described in eukaryotes, while secreted bacterial RBPs have not been reported. Here, we show that the bacterial pathogen Listeria monocytogenes secretes a small RBP that we named Zea. We show that Zea binds a subset of L. monocytogenes RNAs, causing their accumulation in the extracellular medium. Furthermore, during L. monocytogenes infection, Zea binds RIG-I, the non-self-RNA innate immunity sensor, potentiating interferon-β production. Mouse infection studies reveal that Zea affects L. monocytogenes virulence. Together, our results unveil that bacterial RNAs can be present extracellularly in association with RBPs, acting as "social RNAs" to trigger a host response during infection

Les nouveaux États membres face à l'euro : des destins séparés ?.

New member states and the euro: Separate paths? On 1 January 2007, Slovenia became the first of the new member states to adopt the euro. This success might lead us to overlook recent legal and economic debates about the convergence criteria: applying them would place other countries that are trying to join the euro zone in dire macroeconomic straits. Some pundits interpret the maintenance of these criteria as the determination of those already in the euro zone to close their "club" and shut out intruders with weaker economies. As is argued herein, the strict application of these criteria mainly corresponds to a fundamental principle of EU law: equal treatment.Le 1er janvier 2007, la Slovénie est devenue le premier des États nouvellement membres de l'UE à adopter l'euro en tant que monnaie unique. Ce succès cache mal le débat juridique et économique récent autour de l'application des critères de convergence, lesquels placeraient les candidats à l'euro dans des situations macroéconomiques périlleuses. D'aucuns voient alors dans le maintien des NEM hors de la zone euro l'expression de la volonté des États y participant déjà de protéger leur « club » contre l'intrusion de pays dont l'économie est plus faible. Cependant, comme cet article le défend, la rigueur entourant l'application des critères est avant tout l'expression d'un principe fondamental du droit communautaire : l'égalité de traitement.Allemand Frédéric. Les nouveaux États membres face à l'euro : des destins séparés ?.. In: Revue d'études comparatives Est-Ouest, vol. 38, 2007, n°1. Métallurgie et pétrole en Russie. Fondations, ONG et démocratisation. pp. 69-102

Le régime juridique de la dette publique en droit de l'Union Européenne

The public debt is as old as the State. So is the question of its legal framework. At the turn of the 1990s, the Maastricht Treaty renewed the issue. Within the eeconomic and monetary union (EMU), the member states and the Union shall act with respect, in particular, to the guiding principle of sound public finances. The objectification of the capacity to control public debt is achieved through the constitutional enunciation of a new budgetary normality in which the flow and stock of debt are judged on the basis of fixed reference values.This rule of prudence is the basis for surveillance from the dual point of view of investors and other member states. The Maastricht Treaty constitutionalizes the marketization of public debt in connection with the normalization of the status of the State issuer. Although fiscal policy remains a national competence, belonging to the euro zone makes each State responsible to its partners and to the Union. As part of a logic of coordination, this rules-based discipline must prevent and correct any excessive indebtedness. The sovereign debt crisis has undermined the effectiveness of this model and underlines the reluctance of the Union to take over what has become a major issue in the EMU: the public debt. Drawing on the author’s previous work, this thesis identifies the main features of a legal regime for public debt, from its birth to its extinction. as a background, it questions the principle of financial responsibility of the Member States and the possibility of a socialization of public debt.La dette publique est aussi ancienne que l’État. La question de son traitement juridique également. Au tournant des années 1990, le traité de Maastricht renouvelle la problématique. Dans la perspective de l’union économique et monétaire (UEM), les États membres et l’Union doivent agir dans le respect, notamment, du principe directeur de finances publiques saines. L’objectivation de la capacité à maîtriser l’endettement public se réalise à travers l’énonciation constitutionnelle d’une nouvelle normalité budgétaire où le flux et le stock de dette sont jugés à l’aune de valeurs fixes. Cette règle de prudence est au fondement d’une surveillance opérée selon un double point de vue des marchés et des autres États membres. Le traité de Maastricht constitutionnalise la marchéisation de la dette publique en liaison avec la normalisation du statut d’émetteur de l’État. Quoique la politique budgétaire demeure une compétence nationale, l’appartenance à la zone euro responsabilise chaque État vis-à-vis de ses partenaires et de l’Union. S’inscrivant dans une logique de coordination, cette discipline par les règles doit prévenir et corriger tout excès d’endettement. La crise des dettes souveraines déconsidère l’efficacité de ce modèle et souligne la timidité du droit de l’Union à se saisir d’un objet central de l’UEM : la dette publique. S’appuyant sur des travaux antérieurs de l’auteur, cette thèse sur travaux décèle dans les réformes récentes de l’UEM, les lignes d’un régime juridique de la dette publique, de sa naissance à son extinction ; en filigrane, elle interroge l’actualité du principe de responsabilité financière des États membres et la possibilité d’une socialisation de la dette publique

The legal regime of public debt in European Union law

La dette publique est aussi ancienne que l’État. La question de son traitement juridique également. Au tournant des années 1990, le traité de Maastricht renouvelle la problématique. Dans la perspective de l’union économique et monétaire (UEM), les États membres et l’Union doivent agir dans le respect, notamment, du principe directeur de finances publiques saines. L’objectivation de la capacité à maîtriser l’endettement public se réalise à travers l’énonciation constitutionnelle d’une nouvelle normalité budgétaire où le flux et le stock de dette sont jugés à l’aune de valeurs fixes. Cette règle de prudence est au fondement d’une surveillance opérée selon un double point de vue des marchés et des autres États membres. Le traité de Maastricht constitutionnalise la marchéisation de la dette publique en liaison avec la normalisation du statut d’émetteur de l’État. Quoique la politique budgétaire demeure une compétence nationale, l’appartenance à la zone euro responsabilise chaque État vis-à-vis de ses partenaires et de l’Union. S’inscrivant dans une logique de coordination, cette discipline par les règles doit prévenir et corriger tout excès d’endettement. La crise des dettes souveraines déconsidère l’efficacité de ce modèle et souligne la timidité du droit de l’Union à se saisir d’un objet central de l’UEM : la dette publique. S’appuyant sur des travaux antérieurs de l’auteur, cette thèse sur travaux décèle dans les réformes récentes de l’UEM, les lignes d’un régime juridique de la dette publique, de sa naissance à son extinction ; en filigrane, elle interroge l’actualité du principe de responsabilité financière des États membres et la possibilité d’une socialisation de la dette publique.The public debt is as old as the State. So is the question of its legal framework. At the turn of the 1990s, the Maastricht Treaty renewed the issue. Within the eeconomic and monetary union (EMU), the member states and the Union shall act with respect, in particular, to the guiding principle of sound public finances. The objectification of the capacity to control public debt is achieved through the constitutional enunciation of a new budgetary normality in which the flow and stock of debt are judged on the basis of fixed reference values.This rule of prudence is the basis for surveillance from the dual point of view of investors and other member states. The Maastricht Treaty constitutionalizes the marketization of public debt in connection with the normalization of the status of the State issuer. Although fiscal policy remains a national competence, belonging to the euro zone makes each State responsible to its partners and to the Union. As part of a logic of coordination, this rules-based discipline must prevent and correct any excessive indebtedness. The sovereign debt crisis has undermined the effectiveness of this model and underlines the reluctance of the Union to take over what has become a major issue in the EMU: the public debt. Drawing on the author’s previous work, this thesis identifies the main features of a legal regime for public debt, from its birth to its extinction. as a background, it questions the principle of financial responsibility of the Member States and the possibility of a socialization of public debt