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A genetic selection reveals functional metastable structures embedded in a toxin-encoding mRNA [article]

Sara Masachis, Nicolas J Tourasse, Claire Lays, Marion Faucher, Sandrine Chabas, Isabelle Iost, Fabien Darfeuille
2019 bioRxiv   pre-print
Post-transcriptional regulation plays important roles to finely tune gene expression in bacteria. In particular, regulation of type I toxin-antitoxin (TA) systems is achieved through sophisticated mechanisms involving toxin mRNA folding. Here, we set up a genetic approach to decipher the molecular underpinnings behind the regulation of a type I TA in Helicobacter pylori. We used the lethality induced by chromosomal inactivation of the antitoxin to select mutations that suppress toxicity. We
more » ... d that single point mutations are sufficient to allow cell survival. Mutations located either in the 5' untranslated region or within the open reading frame of the toxin hamper its translation by stabilizing stem-loop structures that sequester the Shine-Dalgarno sequence. We propose that these short hairpins correspond to metastable structures that are transiently formed during transcription to avoid premature toxin expression. This work uncovers the co-transcriptional inhibition of translation as an additional layer of TA regulation in bacteria.
doi:10.1101/615682 fatcat:ftjjhphojnhorbcjkrkce5qtrq

Hexose uptake inTrypanosoma cruzi: structure-activity relationship between substrate and transporter

Emmanuel TETAUD, Sandrine CHABAS, Christiane GIROUD, Michael P. BARRETT, Théo BALTZ
1996 Biochemical Journal  
The gene encoding a hexose transporter, TcrHT1, from Trypanosoma cruzi has been functionally expressed in mammalian Chinese hamster ovary cells. Kinetic parameters of the heterologously expressed protein are very similar to those of the transporter identified in T. cruzi epimastigotes, confirming that TcrHT1 is the major transporter functioning in these parasites. A detailed analysis of substrate recognition using analogues of -glucose substituted at each carbon position has been performed.
more » ... glucose transporter of T. cruzi does not recognize C-3 or C-6 analogues of -glucose, whereas these analogues were recognized by the glucose transporter of bloodstream-form T.
doi:10.1042/bj3170353 pmid:8713058 pmcid:PMC1217495 fatcat:7ne6th23gnahjjfktudcrits5q

New forms of HMW MAP2 are preferentially expressed in the spinal cord

Dominique Couchie, Sandrine Chabas, Carmelo Mavilia, Jacques Nunez
1996 FEBS Letters  
200 kDa [17, 18] . Three tubulin binding homologous repeats Abstract The high molecular weight forms of microtubuleassociated protein 2 (MAP2a and b) play a central role in the [19] have been identified, irrespective of the developmental specification of dendrites. RT-PCR amplification of a portion of stage, in the brain MAP2b and MAP2c species. Another the N-terminal and middle MAP2b domains of rat spinal cord LMW variant, MAP2d, with four repeats has been recently cDNAs allowed identification
more » ... of new variants containing both discovered both in the brain [20] and in the neuronal cell line exon 8 (246 bp) and a new exon, 7A (237 bp), located at the ND 7/23 [21] whereas HMW MAP2 forms with four repeats beginning of the middle MAP2b region. The brain and the spinal have been cloned so far only in ND cells [21] and in dorsal cord express transcripts containing exon 8, whereas exon 7A root ganglia [22]. We have recently described [23] a brain alone or exons 7A+8 were detected, whatever the developmental HMW MAP2 variant which differs from MAP2b in the presstage, only in the spinal cord. ence of an insertion of 246 bp in the N-terminal side of the middle region. Key words." Microtubule-associated protein 2; Spinal cord; MAP2b and c are respectively encoded by mRNAs of 9 and New exon 6 kb [24] which are produced by alternative splicing of a primary transcript produced from a single gene [25]. The difference between MAP2a and b is unknown.
doi:10.1016/0014-5793(96)00501-7 pmid:8654594 fatcat:qlhrohcgynfutbilxacjs7pfmy

A genetic selection reveals functional metastable structures embedded in a toxin-encoding mRNA

Sara Masachis, Nicolas J Tourasse, Claire Lays, Marion Faucher, Sandrine Chabas, Isabelle Iost, Fabien Darfeuille
2019 eLife  
Additional information Funding Funder Grant reference number Author Agence Nationale de la Recherche ANR-12-BSV5-0025-Bactox1 Sandrine Chabas Isabelle Iost Fabien Darfeuille  ... 
doi:10.7554/elife.47549 pmid:31411564 pmcid:PMC6733600 fatcat:2cndtnfpjzgqnhmgmbmtcbhszi

Helicobacter pylori Initiates a Mesenchymal Transition through ZEB1 in Gastric Epithelial Cells

Jessica Baud, Christine Varon, Sandrine Chabas, Lucie Chambonnier, Fabien Darfeuille, Cathy Staedel, Yoshio Yamaoka
2013 PLoS ONE  
Chronic Helicobacter pylori infection provokes an inflammation of the gastric mucosa, at high risk for ulcer and cancer development. The most virulent strains harbor the cag pathogenicity island (cagPAI) encoding a type 4 secretion system, which allows delivery of bacterial effectors into gastric epithelial cells, inducing pro-inflammatory responses and phenotypic alterations reminiscent of an epithelial-to-mesenchymal transition (EMT). This study characterizes EMT features in H. pyloriinfected
more » ... gastric epithelial cells, and investigates their relationship with NF-kB activation. Cultured human gastric epithelial cell lines were challenged with a cagPAI+ H. pylori strain or cag isogenic mutants. Morphological changes, epithelial and mesenchymal gene expression and EMT-related microRNAs were studied. H. pylori up-regulates mesenchymal markers, including ZEB1. This transcription factor is prominently involved in the mesenchymal transition of infected cells and its upregulation depends on cagPAI and NF-kB activation. ZEB1 expression and NF-kB activation were confirmed by immunohistochemistry in gastric mucosa from cagPAI+ H. pylori-infected patients. Gastric epithelial cell lines express high miR-200 levels, which are linked to ZEB1 in a reciprocal negative feedback loop and maintain their epithelial phenotype in non-infected conditions. However, miR-200b/c were increased upon infection, despite ZEB1 up-regulation and mesenchymal morphology. In the miR-200b-200a-429 cluster promoter, we identified a functional NF-kB binding site, recruiting NF-kB upon infection and trans-activating the microRNA cluster transcription. In conclusion, in gastric epithelial cells, cagPAI+ H. pylori activates NF-kB, which transactivates ZEB1, subsequently promoting mesenchymal transition. The unexpected N-FkB-dependent increase of miR-200 levels likely thwarts the irreversible loss of epithelial identity in that critical situation.
doi:10.1371/journal.pone.0060315 pmid:23565224 pmcid:PMC3614934 fatcat:5roltgt54bds5nrjvei2ovvyem

The primary transcriptome of the major human pathogen Helicobacter pylori

Cynthia M. Sharma, Steve Hoffmann, Fabien Darfeuille, Jérémy Reignier, Sven Findeiß, Alexandra Sittka, Sandrine Chabas, Kristin Reiche, Jörg Hackermüller, Richard Reinhardt, Peter F. Stadler, Jörg Vogel
2010 Nature  
Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 59 end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and
more » ... ons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ,60 small RNAs including the e-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis-and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
doi:10.1038/nature08756 pmid:20164839 fatcat:linbcircincihktu2buefhq74i

Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression

Cédric Belair, Jessica Baud, Sandrine Chabas, Cynthia M Sharma, Jörg Vogel, Cathy Staedel, Fabien Darfeuille
2011 Silence  
interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression. Abstract Background: MicroRNAs, post-transcriptional regulators of eukaryotic gene expression, are implicated in host defense against pathogens. Viruses and bacteria have evolved strategies that suppress microRNA functions, resulting in a sustainable infection. In this work we report that Helicobacter pylori, a human stomach-colonizing bacterium responsible for severe gastric inflammatory diseases and
more » ... ic cancers, downregulates an embryonic stem cell microRNA cluster in proliferating gastric epithelial cells to achieve cell cycle arrest. Results: Using a deep sequencing approach in the AGS cell line, a widely used cell culture model to recapitulate early events of H. pylori infection of gastric mucosa, we reveal that hsa-miR-372 is the most abundant microRNA expressed in this cell line, where, together with hsa-miR-373, it promotes cell proliferation by silencing large tumor suppressor homolog 2 (LATS2) gene expression. Shortly after H. pylori infection, miR-372 and miR-373 synthesis is highly inhibited, leading to the post-transcriptional release of LATS2 expression and thus, to a cell cycle arrest at the G1/S transition. This downregulation of a specific cell-cycle-regulating microRNA is dependent on the translocation of the bacterial effector CagA into the host cells, a mechanism highly associated with the development of severe atrophic gastritis and intestinal-type gastric carcinoma. Conclusions: These data constitute a novel example of host-pathogen interplay involving microRNAs, and unveil the couple LATS2/miR-372 and miR-373 as an unexpected mechanism in infection-induced cell cycle arrest in proliferating gastric cells, which may be relevant in inhibition of gastric epithelium renewal, a major host defense mechanism against bacterial infections.
doi:10.1186/1758-907x-2-7 pmid:22027184 pmcid:PMC3212895 fatcat:7k3bhqvhebf7tjqcs3zd5jdbda

Structural insights into the AapA1 toxin of Helicobacter pylori

Dursun Nizam Korkut, Isabel D. Alves, Alexander Vogel, Sandrine Chabas, Cynthia M. Sharma, Denis Martinez, Antoine Loquet, Gilmar F. Salgado, Fabien Darfeuille
2019 Biochimica et Biophysica Acta - General Subjects  
We previously reported the identification of the aapA1/IsoA1 locus as part of a new family of toxin-antitoxin (TA) systems in the human pathogen Helicobacter pylori. AapA1 belongs to type I TA bacterial toxins, and both its mechanism of action towards the membrane and toxicity features are still unclear.
doi:10.1016/j.bbagen.2019.129423 pmid:31476357 fatcat:5atessqqe5edrp7rv4xr6etiz4

Mechanistic insights into type I toxin antitoxin systems inHelicobacter pylori:the importance of mRNA folding in controlling toxin expression

Hélène Arnion, Dursun Nizam Korkut, Sara Masachis Gelo, Sandrine Chabas, Jérémy Reignier, Isabelle Iost, Fabien Darfeuille
2017 Nucleic Acids Research  
Type I toxin-antitoxin (TA) systems have been identified in a wide range of bacterial genomes. Here, we report the characterization of a new type I TA system present on the chromosome of the major human gastric pathogen, Helicobacter pylori. We show that the aapA1 gene encodes a 30 amino acid peptide whose artificial expression in H. pylori induces cell death. The synthesis of this toxin is prevented by the transcription of an antitoxin RNA, named IsoA1, expressed on the opposite strand of the
more » ... oxin gene. We further reveal additional layers of posttranscriptional regulation that control toxin expression: (i) transcription of the aapA1 gene generates a full-length transcript whose folding impedes translation (ii) a 3 end processing of this message generates a shorter transcript that, after a structural rearrangement, becomes translatable (iii) but this rearrangement also leads to the formation of two stemloop structures allowing formation of an extended duplex with IsoA1 via kissing-loop interactions. This interaction ensures both the translation inhibition of the AapA1 active message and its rapid degradation by RNase III, thus preventing toxin synthesis under normal growth conditions. Finally, a search for homologous mRNA structures identifies similar TA systems in a large number of Helicobacter and Campylobacter genomes.
doi:10.1093/nar/gkw1343 pmid:28077560 pmcid:PMC5416894 fatcat:3nneltkkuncozj5gzpanthm7fy

Molecular basis of differential target regulation by miR-96 and miR-182: the Glypican-3 as a model

Sandra Jalvy-Delvaille, Marion Maurel, Vanessa Majo, Nathalie Pierre, Sandrine Chabas, Chantal Combe, Jean Rosenbaum, Francis Sagliocco, Christophe F. Grosset
2011 Nucleic Acids Research  
Besides the fact that miR-96 and miR-182 belong to the miR-182/183 cluster, their seed region (UUGGCA, nucleotides 2-7) is identical suggesting potential common properties in mRNA target recognition and cellular functions. Here, we used the mRNA encoding Glypican-3, a heparan-sulfate proteoglycan, as a model target as its short 3 0 untranslated region is predicted to contain one miR-96/182 site, and assessed whether it is post-transcriptionally regulated by these two microRNAs. We found that
more » ... -96 downregulated GPC3 expression by targeting its mRNA 3 0 -untranslated region and interacting with the predicted site. This downregulatory effect was due to an increased mRNA degradation and depended on Argonaute-2. Despite its seed similarity with miR-96, miR-182 was unable to regulate GPC3. This differential regulation was confirmed on two other targets, FOXO1 and FN1. By site-directed mutagenesis, we demonstrated that the miRNA nucleotide 8, immediately downstream the UUGGCA seed, plays a critical role in target recognition by miR-96 and miR-182. Our data suggest that because of a base difference at miRNA position 8, these two microRNAs control a completely different set of genes and therefore are functionally independent.
doi:10.1093/nar/gkr843 pmid:22009679 pmcid:PMC3273822 fatcat:2sndildisjgmzbqu6nnytefoga

NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients

Sylvie Rusakiewicz, Aurélie Perier, Michaela Semeraro, Jonathan M. Pitt, Elke Pogge von Strandmann, Katrin S. Reiners, Sandrine Aspeslagh, Christelle Pipéroglou, Frédéric Vély, Alexandre Ivagnes, Sarah Jegou, Niels Halama (+32 others)
2016 Oncoimmunology  
Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions
more » ... NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST. Phenotypes based on disbalanced NKp30B/NKp30C ratio (DBC low ) and low expression levels of NKp30A were identified in one third of patients with dismal prognosis across molecular subtypes. This DBC low blood phenotype was associated with a pro-inflammatory and immunosuppressive tumor microenvironment. In addition, detectable levels of the NKp30 ligand sB7-H6 predicted a worse prognosis in metastatic GIST. Soluble BAG6, an alternate ligand for NKp30 was associated with low NKp30 transcription and had additional predictive value in GIST patients with high NKp30 expression. Such GIST microenvironments could be rescued by therapy based on rIFN-a and anti-TRAIL mAb which reinstated innate immunity.
doi:10.1080/2162402x.2015.1137418 pmid:28197361 pmcid:PMC5283614 fatcat:ubv2gwxdwzd2jami7mnkor6cfm

Littérature et valeurs

Lydie Laroque, Caroline Raulet-Marcel
2017 Le Français aujourd hui  
Chabas, et le rôle de l'enseignant pour amener les élèves à envisager la fonction idéologique d'un texte.  ...  Dans le même esprit, la contribution de Virginie Brinker et Sandrine Meslet montre comment une classe de Quatrième, en étudiant la pièce de Maïssa Bey, Tu vois c'que j'veux dire ?  ... 
doi:10.3917/lfa.197.0005 fatcat:ba3iafpj75egzp7phl57rtpppi

المسئولیة التقصیریة لناشرى برامج التبادل غیر المشروع للمصنفات الفکریة بتقنیة (Peer-to-peer) دراسة مقارنة فی القانون الفرنسى والمصرى والعُمانى

عبدالهادى فوزى العوضى
2019 مجلة القانون والاقتصاد  
ف‬ ‫الزيارل‬ ‫تمت‬ 15 / 12 / 2015 . (2) Sandrine HALLEMANS, Rapport préc., pp. 14 et 15. (3) V. S. VON LEWINSKI, art. préc., pp. 2 et 3.  ...  Donkey e Fast Track, 2000 2 ‫ـئان‬ ‫وــ‬ ‫ـ‬ ‫ت‬ ‫ـرت‬ ‫انتشــ‬ ‫ـد‬ ‫وقــ‬ ‫ـا‬ ‫كنولوجيــ‬ ‫ـات‬ ‫الملفــ‬ ‫ـادل‬ ‫تبــ‬ ‫ال‬ ‫ـبإلات‬ ‫شــ‬ ‫ـر‬ ‫موــ‬ ‫ـة‬ ‫الرقميــ‬ (1)Sandrine HALLEMANS, « Etude  ...  CHABAS, Montchrestien, 1996, no 343, p. 464. ( 6 ‫حم‬ ‫صبرى‬ ‫د.‬ ‫  ... 
doi:10.21608/mle.2019.110343 fatcat:6oeyfarvqnao5otxhgmsjgbgja

Curriculum vitae Impreso normalizado

Ministerio De Educación, Y Cultura, Deporte
REVISTA/LIBRO: Adrian Bieniec, Szilvia Lengl, Sandrine Okou, Natalia Shchyhlebska (eds.), Rem tene, verba sequentur! Gelebte Interkulturalität. Festschrift zum 65.  ...  REVISTA/LIBRO: Dianium, IV (Homenaje a Juan Chabás), página inicial y página final:293-299 (1989). CLAVE: A AUTORES (p.o. de firma): Tomás Albaladejo Mayordomo TÍTULO: Retórica. REF.  ... 

Low-level Analysis of High-density Oligonucleotide Array Data: Background, Normalization and Summarization Low-level Analysis of High-density Oligonucleotide Array Data: Background, Normalization and Summarization

Benjamin Bolstad, Benjamin Bolstad, Benjamin Bolstad, Terence Speed
2004 unpublished
I owe a debt of gratitude to Sandrine Dudoit and Jean Yee Hwa Yang for recruiting me to work on SMA without which I may not have got involved in microarray data analysis.  ...  A number of microarray studies have used pooling including Crnogorac-Jurcevic et al. (2002), Zhu et al. (2003), Chabas et al. (2001), Waring et al. (2001), Saban et al. (2001), Enard et al. (2002) and  ... 
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