94 research outputs found
Dynamique des facteurs pré-ribosomiques au cours de la biogenÚse de la grande sous-unité ribosomique chez S. cerevisiae
This work focuses on the dynamics of assembly, dissociation and recycling of proteins involved in the biogenesis of the large ribosomal subunit in Saccharomyces cerevisiae. It sheds some light on two control points in this metabolic pathway, localised in the nucleus and the cytoplasm respectively.We have shown that the nuclear protein Nsa2, which is very conserved throughout the eukaryotic kingdom, is required for the correct maturation of the 27SB ribosomal RNA precursor. Nsa2 is an unstable factor, regulated in correlation with the activity of ribosome biogenesis; it thus constitutes a good candidate for the integration of various signals resulting in the regulation of this metabolic pathway. Besides, using the SILAC technique, we could define groups of early or late acting factors relative to the Nsa2 action time.In the cytoplasm, we identified a protein network, which marks the end of ribosome biogenesis and triggers the entry of new ribosomal subunits into translation. The cytoplasmic protein Rei1 and the karyopherin Kap121 are both required for the recycling from the cytoplasm to the nucleus of a dimer of shuttling factors, Arx1-Alb1. This recycling enables the dissociation of the anti-association factor Tif6 from the large ribosomal subunit, which can consequently bind the small ribosomal subunit and enter translation.Les travaux de ce mĂ©moire portent sur la dynamique d'assemblage, de dissociation et de recyclage des protĂ©ines impliquĂ©es dans la biogenĂšse de la grande sous-unitĂ© ribosomique chez la levure Saccharomyces cerevisiae. Ils permettent une meilleure comprĂ©hension de deux points de contrĂŽle de cette voie mĂ©tabolique, l'un dans le noyau, l'autre dans le cytoplasme. Nous avons montrĂ© que la protĂ©ine nuclĂ©aire Nsa2, extrĂȘmement conservĂ©e chez les Eucaryotes, est requise pour la maturation correcte de l'intermĂ©diaire d'ARN ribosomique 27SB. Nsa2 est un facteur instable et rĂ©gulĂ© en fonction de l'activitĂ© de la biogenĂšse des ribosomes ; Ă ce titre, il pourrait centraliser diffĂ©rents signaux de contrĂŽle de la voie mĂ©tabolique. Par ailleurs, la technique de SILAC nous a permis de dĂ©finir des groupes de facteurs prĂ©-ribosomiques prĂ©coces ou tardifs par rapport au point d'action de Nsa2.Dans le cytoplasme, nous avons mis en Ă©vidence un rĂ©seau de protĂ©ines marquant la transition entre la fin de la biogenĂšse de la grande sous-unitĂ© et l'initiation de la traduction. La protĂ©ine cytoplasmique Rei1 et la karyophĂ©rine Kap121 sont requises pour le recyclage du dimĂšre de facteurs navettes Arx1-Alb1, du cytoplasme vers le noyau. Ce recyclage conditionne la dissociation entre le facteur d'anti-association Tif6 et la grande sous-unitĂ© ribosomique, qui peut dĂšs lors se lier Ă la petite sous-unitĂ© ribosomique et participer Ă la traduction
La mise en Ă©vidence du bacille de la peste, Hong-Kong 1894
Bien quâelle ait dĂ©cimĂ© des millions de personnes au cours des siĂšcles, la peste ne constitue plus aujourdâhui un problĂšme majeur de santĂ© publique. Transmise par les puces, cette maladie affecte surtout les petits animaux, et peut occasionnellement ĂȘtre transmise Ă lâhomme. Selon les chiffres de lâOrganisation Mondiale de la SantĂ©, le nombre de cas humains en 2003 Ă©tait de 2118, dont 182 mortels.Comment cette maladie tristement cĂ©lĂšbre est-elle passĂ©e, en un siĂšcle, du rang de flĂ©au de lâhumanitĂ© Ă celui de pathologie rare et relativement bien contrĂŽlĂ©e ? La description prĂ©cise de la bactĂ©rie par le mĂ©decin franco-suisse Alexandre Yersin, a Ă©tĂ© Ă la base de ce progrĂšs : elle sera nommĂ©e Yersinia pestis en son honneur. Suite Ă ses travaux, les recherches se concentrĂšrent sur les moyens de soigner les malades par des sĂ©rothĂ©rapies et lâadministration dâantibiotiques, et de protĂ©ger de lâaffection par la mise au point de vaccins. Si, grĂące Ă ces mesures, la peste nâest donc plus Ă proprement parler un sujet dâactualitĂ©, la mĂ©thodologie qui a conduit Yersin Ă sa dĂ©couverte est toujours pertinente lorsque les scientifiques sont confrontĂ©s Ă une nouvelle Ă©pidĂ©mie et cherchent Ă en identifier les causes. Ainsi, ces derniĂšres annĂ©es, le mĂȘme type de dĂ©marche a-t-il Ă©tĂ© mis en place afin dâĂ©tudier des maladies Ă©mergentes comme le SIDA, le SRAS, le chikungunya ou encore le virus Ăbola.Although the plague has claimed the life of millions of people over the centuries, it no longer poses a major risk to public health. Spread by fleas, the disease mainly infects small animals, and can occasionally be transmitted to humans. According to figures released by the World Health Organization, 2,118 cases of human plague were reported in 2003, of which 182 were fatal.How, in the space of a century, did this notorious disease go from being the scourge of humanity to a rare and relatively well-controlled pathology? The key to this advance was the detailed description of the bacteria by the Franco-Swiss doctor Alexandre Yersin: the bacteria was named Yersinia pestis in his honour. Following Yersinâs work, research was oriented towards antiserum treatment, the administration of antibiotics, and the prevention of infection through the development of vaccines.Thanks to these measures, the plague is no longer in the news. Yet the methodology that led Yersin to make his discovery remains relevant whenever scientists are confronted with a new epidemic and attempt to identify its causes. Thus, in recent years, the same type of approach has been used to study emerging diseases such as AIDS, SARS, Chikungunya and the Ebola virus
A functional network involved in the recycling of nucleocytoplasmic pre-60S factors
Eukaryotic pre-ribosomes go through cytoplasmic maturation steps before entering translation. The nucleocytoplasmic proteins participating in these late stages of maturation are reimported to the nucleus. In this study, we describe a functional network focused on Rei1/Ybr267w, a strictly cytoplasmic pre-60S factor indirectly involved in nuclear 27S pre-ribosomal RNA processing. In the absence of Rei1, the nuclear import of at least three other pre-60S factors is impaired. The accumulation in the cytoplasm of a small complex formed by the association of Arx1 with a novel factor, Alb1/Yjl122w, inhibits the release of the putative antiassociation factor Tif6 from the premature large ribosomal subunits and its recycling to the nucleus. We propose a model in which Rei1 is a key factor for the coordinated dissociation and recycling of the last pre-60S factors before newly synthesized large ribosomal subunits enter translation
60S ribosomal subunit assembly dynamics defined by semi-quantitative mass spectrometry of purified complexes
During the highly conserved process of eukaryotic ribosome formation, RNA follows a maturation path with well-defined, successive intermediates that dynamically associate with many pre-ribosomal proteins. A comprehensive description of the assembly process is still lacking. To obtain data on the timing and order of association of the different pre-ribosomal factors, a strategy consists in the use of pre-ribsomal particles isolated from mutants that block ribosome formation at different steps. Immunoblots, inherently limited to only a few factors, have been applied to evaluate the accumulation or decrease of pre-ribosomal intermediates under mutant conditions. For a global protein-level description of different 60S ribosomal subunit maturation intermediates in yeast, we have adapted a method of in vivo isotopic labelling and mass spectrometry to study pre-60S complexes isolated from strains in which rRNA processing was affected by individual depletion of five factors: Ebp2, Nog1, Nsa2, Nog2 or Pop3. We obtained quantitative data for 45 distinct pre-60S proteins and detected coordinated changes for over 30 pre-60S factors in the analysed mutants. These results led to the characterisation of the composition of early, intermediate and late pre-ribosomal complexes, specific for crucial maturation steps during 60S assembly in eukaryotes
A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response
International audienceIntracellular pathogens such as subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate interferon IFN-stimulated genes (ISGs). IFN- expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with -expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1 mice or when was constitutively expressed. Thus, the LntA-BAHD1 interplay may modulate IFN--mediated immune response to control bacterial colonization of the host
Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.
BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO) placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi). In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases
Exo-zodi Modeling for the Large Binocular Telescope Interferometer
Habitable zone dust levels are a key unknown that must be understood to ensure the success of future space missions to image Earth analogs around nearby stars. Current detection limits are several orders of magnitude above the level of the solar system's zodiacal cloud, so characterization of the brightness distribution of exo-zodi down to much fainter levels is needed. To this end, the Large Binocular Telescope Interferometer (LBTI) will detect thermal emission from habitable zone exo-zodi a few times brighter than solar system levels. Here we present a modeling framework for interpreting LBTI observations, which yields dust levels from detections and upper limits that are then converted into predictions and upper limits for the scattered light surface brightness. We apply this model to the HOSTS survey sample of nearby stars; assuming a null depth uncertainty of 10^(â4) the LBTI will be sensitive to dust a few times above the solar system level around Sun-like stars, and to even lower dust levels for more massive stars
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-ÎČ 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
La Cappadoce méridionale de la Préhistoire à l'époque byzantine
Il y a environ 25 ans, Olivier Pelon organisait Ă lâInstitut Français dâĂtudes Anatoliennes dâIstanbul un colloque destinĂ© Ă faire lâĂ©tat des recherches sur la Cappadoce mĂ©ridionale jusquâĂ la fin de lâĂ©poque romaine. Un quart de siĂšcle aprĂšs ce premier colloque, il Ă©tait intĂ©ressant de faire un nouveau point sur lâavancĂ©e des recherches dans cette Cappadoce mĂ©ridionale, de la prĂ©histoire Ă la pĂ©riode byzantine. Ce nouveau colloque, placĂ© cette fois encore sous lâĂ©gide de lâInstitut Français dâĂtudes Anatoliennes et intĂ©grĂ© Ă la sĂ©rie des Rencontres dâarchĂ©ologie de lâIFEA rĂ©unit vingt-trois communications. Si les pĂ©riodes nĂ©olithique et chalcolithique ont Ă©tĂ© particuliĂšrement bien reprĂ©sentĂ©es, ce qui tĂ©moigne bien de lâimportance de cette phase de la prĂ©histoire cappadocienne, liĂ©e aux gisements dâobsidienne des Melendiz DaÄları, on soulignera en revanche lâabsence presque totale du Bronze Ancien. Cette phase est en effet peu reprĂ©sentĂ©e dans lâarchĂ©ologie locale. La mĂȘme remarque peut sâappliquer au Bronze Moyen. La fin du Bronze Moyen, fort heureusement, est reprĂ©sentĂ©e Ă Porsuk, de mĂȘme que le Bronze RĂ©cent qui bĂ©nĂ©ficie, depuis peu, tout comme lâĂge du Fer, du dĂ©marrage fructueux des fouilles de Kınık HöyĂŒk. Enfin, lâAntiquitĂ© tardive et Byzance ont pu ĂȘtre reprĂ©sentĂ©es, principalement autour de Tyane, ce qui nâavait pas pu ĂȘtre le cas lors du premier colloque. En octobre 2012, quelques semaines avant la tenue de la Rencontre, on apprenait malheureusement le dĂ©cĂšs brutal et inattendu dâOlivier Pelon, ancien directeur de la mission de Porsuk (jusquâen 2002) et organisateur de ce premier colloque cappadocien. Câest bien en hommage Ă sa mĂ©moire que notre Rencontre cappadocienne de 2012 et sa publication ont Ă©tĂ© naturellement dĂ©diĂ©es
Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats
In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Developmentâs (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security
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