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Accueil > Publications

Publications Département Biologie des Génomes

2017



  • S. Barral, Y. Morozumi, H. Tanaka, E. Montellier, J. Govin, M. de Dieuleveult, G. Charbonnier, Y. Couté, D. Puthier, T. Buchou, F. Boussouar, T. Urahama, F. Fenaille, S. Curtet, P. Héry, N. Fernandez-Nunez, H. Shiota, M. Gérard, S. Rousseaux, H. Kurumizaka, et S. Khochbin, « Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells », Molecular Cell, vol. 66, nᵒ 1, p. 89-101.e8, 2017.

  • L. Bidou, O. Bugaud, V. Belakhov, T. Baasov, et O. Namy, « Characterization of new-generation aminoglycoside promoting premature termination codon readthrough in cancer cells », RNA biology, p. 1-11, 2017.
    Résumé : Nonsense mutations, generating premature termination codons (PTCs), account for 10% to 30% of the mutations in tumor suppressor genes. Nonsense translational suppression, induced by small molecules including gentamicin and G418, has been suggested as a potential therapy to counteract the deleterious effects of nonsense mutations in several genetic diseases and cancers. We describe here that NB124, a synthetic aminoglycoside derivative recently developed especially for PTC suppression, strongly induces apoptosis in human tumor cells by promoting high level of PTC readthrough. Using a reporter system, we showed that NB124 suppressed several of the PTCs encountered in tumor suppressor genes, such as the p53 and APC genes. We also showed that NB124 counteracted p53 mRNA degradation by nonsense-mediated decay (NMD). Both PTC suppression and mRNA stabilization contributed to the production of a full-length p53 protein capable of activating p53-dependent genes, thereby specifically promoting high levels of apoptosis. This new-generation aminoglycoside thus outperforms the only clinically available readthrough inducer (gentamicin). These results have important implications for the development of personalised treatments of PTC-dependent diseases and for the development of new drugs modifying translation fidelity.
    Mots-clés : Aminoglycoside, Apoptosis, cancer, DBG, GST, p53, stop codon readthrough.


  • W. V. Bienvenut, J. - P. Scarpelli, J. Dumestier, T. Meinnel, et C. Giglione, « EnCOUNTer: a parsing tool to uncover the mature N-terminus of organelle-targeted proteins in complex samples », BMC Bioinformatics, vol. 18, nᵒ 1, 2017.
    Mots-clés : DBG, DIR, PROMTI, SICS.

  • M. Boudard, D. Barth, J. Bernauer, A. Denise, et J. Cohen, « GARN2: coarse-grained prediction of 3D structure of large RNA molecules by regret minimization », Bioinformatics (Oxford, England), 2017.
    Résumé : Motivation: Predicting the 3D structure of RNA molecules is a key feature towards predicting their functions. Methods which work at atomic or nucleotide level are not suitable for large molecules. In these cases, coarse-grained prediction methods aim to predict a shape which could be refined later by using more precise methods on smaller parts of the molecule. Results: We developed a complete method for sampling 3D RNA structure at a coarse-grained model, taking a secondary structure as input. One of the novelties of our method is that a second step extracts two best possible structures close to the native, from a set of possible structures. Although our method benefits from the first version of GARN, some of the main features on GARN2 are very different. GARN2 is much faster than the previous version and than the well-known methods of the state-of-art. Our experiments show that GARN2 can also provide better structures than the other state-of-the-art methods. Availability and implementations: GARN2 is written in Java. It is freely distributed and available at: http://garn.lri.fr/ . Contacts: melanie.boudard@lri.fr , johanne.cohen@lri.fr. Supplementary information: Supplementary data are available at Bioinformatics online.
    Mots-clés : BIM, DBG.

  • E. Dubois, N. Mathy, V. Régnier, J. Bischerour, C. Baudry, R. Trouslard, et M. Bétermier, « Multimerization properties of PiggyMac, a domesticated piggyBac transposase involved in programmed genome rearrangements », Nucleic Acids Research, 2017.
    Résumé : During sexual processes, the ciliate Paramecium eliminates 25-30% of germline DNA from its somatic genome. DNA elimination includes excision of ∼45 000 short, single-copy internal eliminated sequences (IESs) and depends upon PiggyMac (Pgm), a domesticated piggyBac transposase that is essential for DNA cleavage at IES ends. Pgm carries a core transposase region with a putative catalytic domain containing three conserved aspartic acids, and a downstream cysteine-rich (CR) domain. A C-terminal extension of unknown function is predicted to adopt a coiled-coil (CC) structure. To address the role of the three domains, we designed an in vivo complementation assay by expressing wild-type or mutant Pgm-GFP fusions in cells depleted for their endogenous Pgm. The DDD triad and the CR domain are essential for Pgm activity and mutations in either domain have a dominant-negative effect in wild-type cells. A mutant lacking the CC domain is partially active in the presence of limiting Pgm amounts, but inactive when Pgm is completely absent, suggesting that presence of the mutant protein increases the overall number of active complexes. We conclude that IES excision involves multiple Pgm subunits, of which at least a fraction must contain the CC domain.
    Mots-clés : DBG, DSMC, MICMAC.


  • B. Felden et P. Bouloc, « Regulatory RNAs in bacteria: From identification to function », Methods, vol. 117, p. 1-2, 2017.


  • S. Fieulaine, R. Alves de Sousa, L. Maigre, K. Hamiche, M. Alimi, J. - M. Bolla, A. Taleb, A. Denis, J. - M. Pagès, I. Artaud, T. Meinnel, et C. Giglione, « Corrigendum: A unique peptide deformylase platform to rationally design and challenge novel active compounds », Scientific Reports, vol. 7, p. 39365, janv. 2017.


  • E. Galli, C. Midonet, E. Paly, et F. - X. Barre, « Fast growth conditions uncouple the final stages of chromosome segregation and cell division in Escherichia coli », PLOS Genetics, vol. 13, nᵒ 3, p. e1006702, mars 2017.


  • E. Galli, E. Paly, et F. - X. Barre, « Late assembly of the Vibrio cholerae cell division machinery postpones septation to the last 10% of the cell cycle », Scientific Reports, vol. 7, p. 44505, mars 2017.

  • J. Gruchota, C. Denby Wilkes, O. Arnaiz, L. Sperling, et J. K. Nowak, « A meiosis-specific Spt5 homolog involved in non-coding transcription », Nucleic Acids Research, 2017.
    Résumé : Spt5 is a conserved and essential transcriptional regulator that binds directly to RNA polymerase and is involved in transcription elongation, polymerase pausing and various co-transcriptional processes. To investigate the role of Spt5 in non-coding transcription, we used the unicellular model Paramecium tetraurelia In this ciliate, development is controlled by epigenetic mechanisms that use different classes of non-coding RNAs to target DNA elimination. We identified two SPT5 genes. One (STP5v) is involved in vegetative growth, while the other (SPT5m) is essential for sexual reproduction. We focused our study on SPT5m, expressed at meiosis and associated with germline nuclei during sexual processes. Upon Spt5m depletion, we observed absence of scnRNAs, piRNA-like 25 nt small RNAs produced at meiosis. The scnRNAs are a temporal copy of the germline genome and play a key role in programming DNA elimination. Moreover, Spt5m depletion abolishes elimination of all germline-limited sequences, including sequences whose excision was previously shown to be scnRNA-independent. This suggests that in addition to scnRNA production, Spt5 is involved in setting some as yet uncharacterized epigenetic information at meiosis. Our study establishes that Spt5m is crucial for developmental genome rearrangements and necessary for scnRNA production.
    Mots-clés : ANGE, DBG.

  • H. Lalucque, F. Malagnac, K. Green, V. Gautier, P. Grognet, L. Chan Ho Tong, B. Scott, et P. Silar, « IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina », Developmental Biology, vol. 421, nᵒ 2, p. 126-138, 2017.
    Résumé : Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures.
    Mots-clés : DBG, Developmental mutants, DSMC, Fungal development, Multicellular fruiting bodies, Perithecium, Podospora anserina.

  • J. Lehmann, « Induced fit of the peptidyl-transferase center of the ribosome and conformational freedom of the esterified amino acids », RNA (New York, N.Y.), vol. 23, nᵒ 2, p. 229-239, 2017.
    Résumé : The catalytic site of most enzymes can efficiently handle only one substrate. In contrast, the ribosome is capable of polymerizing at a similar rate at least 20 different kinds of amino acids from aminoacyl-tRNA carriers while using just one catalytic site, the peptidyl-transferase center (PTC). An induced-fit mechanism has been uncovered in the PTC, but a possible connection between this mechanism and the uniform handling of the substrates has not been investigated. We present an analysis of published ribosome structures supporting the hypothesis that the induced fit eliminates unreactive rotamers predominantly populated for some A-site aminoacyl esters before induction. We show that this hypothesis is fully consistent with the wealth of kinetic data obtained with these substrates. Our analysis reveals that induction constrains the amino acids into a reactive conformation in a side-chain independent manner. It allows us to highlight the rationale of the PTC structural organization, which confers to the ribosome the very unusual ability to handle large as well as small substrates.
    Mots-clés : aminoacyl-tRNA, DBG, EF-P, induced fit, peptidyl-transferase center, Ribosome, SSFA.


  • B. Michel et S. J. Sandler, « Replication Restart in Bacteria », Journal of Bacteriology, p. JB.00102-17, mars 2017.

  • B. Michel et A. K. Sinha, « The inactivation of rfaP, rarA or sspA gene improves the viability of the Escherichia coli DNA polymerase III holD mutant », Molecular Microbiology, 2017.
    Résumé : The Escherichia coli holD mutant is poorly viable because the stability of holoenzyme polymerase III (Pol III HE) on DNA is compromised. Consequently, the SOS response is induced and the SOS polymerases DinB and Pol II further hinder replication. Mutations that restore the holD mutant viability belong to two classes, those that stabilize Pol III on DNA and those that prevent the deleterious effects of DinB over-production. We identified a dnaX mutation and the inactivation of rfaP and sspA genes as belonging to the first class of holD mutant suppressors. dnaX encodes a Pol III clamp loader subunit that interacts with HolD. rfaP encodes a lipopolysaccharide kinase that acts in outer membrane biogenesis. Its inactivation improves the holD mutant growth in part by affecting potassium import, previously proposed to stabilize Pol III HE on DNA by increasing electrostatic interactions. sspA encodes a global transcriptional regulator and growth of the holD mutant in its absence suggests that SspA controls genes that affect protein-DNA interactions. The inactivation of rarA belongs to the second class of suppressor mutations. rarA inactivation has a weak effect but is additive with other suppressor mutations. Our results suggest that RarA facilitates DinB binding to abandoned forks.
    Mots-clés : DBG, STABAC.

  • M. Mirande, « The Aminoacyl-tRNA Synthetase Complex », Sub-Cellular Biochemistry, vol. 83, p. 505-522, 2017.
    Résumé : Aminoacyl-tRNA synthetases (AARSs) are essential enzymes that specifically aminoacylate one tRNA molecule by the cognate amino acid. They are a family of twenty enzymes, one for each amino acid. By coupling an amino acid to a specific RNA triplet, the anticodon, they are responsible for interpretation of the genetic code. In addition to this translational, canonical role, several aminoacyl-tRNA synthetases also fulfill nontranslational, moonlighting functions. In mammals, nine synthetases, those specific for amino acids Arg, Asp, Gln, Glu, Ile, Leu, Lys, Met and Pro, associate into a multi-aminoacyl-tRNA synthetase complex, an association which is believed to play a key role in the cellular organization of translation, but also in the regulation of the translational and nontranslational functions of these enzymes. Because the balance between their alternative functions rests on the assembly and disassembly of this supramolecular entity, it is essential to get precise insight into the structural organization of this complex. The high-resolution 3D-structure of the native particle, with a molecular weight of about 1.5 MDa, is not yet known. Low-resolution structures of the multi-aminoacyl-tRNA synthetase complex, as determined by cryo-EM or SAXS, have been reported. High-resolution data have been reported for individual enzymes of the complex, or for small subcomplexes. This review aims to present a critical view of our present knowledge of the aminoacyl-tRNA synthetase complex in 3D. These preliminary data shed some light on the mechanisms responsible for the balance between the translational and nontranslational functions of some of its components.
    Mots-clés : Aminoacyl-tRNA synthetase (AARS), Core synthetases, Crystal Structure, DBG, MARS, MSC assembly, Multi-aminacyl-tRNA synthetase complex (MSC).

  • R. I. Ponce-Toledo, P. Deschamps, P. López-García, Y. Zivanovic, K. Benzerara, et D. Moreira, « An Early-Branching Freshwater Cyanobacterium at the Origin of Plastids », Current biology: CB, vol. 27, nᵒ 3, p. 386-391, 2017.
    Résumé : Photosynthesis evolved in eukaryotes by the endosymbiosis of a cyanobacterium, the future plastid, within a heterotrophic host. This primary endosymbiosis occurred in the ancestor of Archaeplastida, a eukaryotic supergroup that includes glaucophytes, red algae, green algae, and land plants [1-4]. However, although the endosymbiotic origin of plastids from a single cyanobacterial ancestor is firmly established, the nature of that ancestor remains controversial: plastids have been proposed to derive from either early- or late-branching cyanobacterial lineages [5-11]. To solve this issue, we carried out phylogenomic and supernetwork analyses of the most comprehensive dataset analyzed so far including plastid-encoded proteins and nucleus-encoded proteins of plastid origin resulting from endosymbiotic gene transfer (EGT) of primary photosynthetic eukaryotes, as well as wide-ranging genome data from cyanobacteria, including novel lineages. Our analyses strongly support that plastids evolved from deep-branching cyanobacteria and that the present-day closest cultured relative of primary plastids is Gloeomargarita lithophora. This species belongs to a recently discovered cyanobacterial lineage widespread in freshwater microbialites and microbial mats [12, 13]. The ecological distribution of this lineage sheds new light on the environmental conditions where the emergence of photosynthetic eukaryotes occurred, most likely in a terrestrial-freshwater setting. The fact that glaucophytes, the first archaeplastid lineage to diverge, are exclusively found in freshwater ecosystems reinforces this hypothesis. Therefore, not only did plastids emerge early within cyanobacteria, but the first photosynthetic eukaryotes most likely evolved in terrestrial-freshwater settings, not in oceans as commonly thought.
    Mots-clés : chloroplasts, Cyanobacteria, DBG, evolution, molecular phylogeny, phylogenomics, Plastids, RBA.


  • W. V. Bienvenut, C. Giglione, et T. Meinnel, « SILProNAQ: A Convenient Approach for Proteome-Wide Analysis of Protein N-Termini and N-Terminal Acetylation Quantitation », in Protein Terminal Profiling, vol. 1574, O. Schilling, Éd. New York, NY: Springer New York, 2017, p. 17-34.


  • C. Voisset, M. Blondel, G. W. Jones, G. Friocourt, G. Stahl, S. Chédin, V. Beringue, et R. Gillet, « The double life of the ribosome: when its protein folding activity supports prion propagation », Prion, p. 00-00, mars 2017.

  • S. Wang, T. Hassold, P. Hunt, M. A. White, D. Zickler, N. Kleckner, et L. Zhang, « Inefficient Crossover Maturation Underlies Elevated Aneuploidy in Human Female Meiosis », Cell, vol. 168, nᵒ 6, p. 977-989.e17, 2017.
    Résumé : Meiosis is the cellular program that underlies gamete formation. For this program, crossovers between homologous chromosomes play an essential mechanical role to ensure regular segregation. We present a detailed study of crossover formation in human male and female meiosis, enabled by modeling analysis. Results suggest that recombination in the two sexes proceeds analogously and efficiently through most stages. However, specifically in female (but not male), ∼25% of the intermediates that should mature into crossover products actually fail to do so. Further, this "female-specific crossover maturation inefficiency" is inferred to make major contributions to the high level of chromosome mis-segregation and resultant aneuploidy that uniquely afflicts human female oocytes (e.g., giving Down syndrome). Additionally, crossover levels on different chromosomes in the same nucleus tend to co-vary, an effect attributable to global per-nucleus modulation of chromatin loop size. Maturation inefficiency could potentially reflect an evolutionary advantage of increased aneuploidy for human females.
    Mots-clés : DBG, DSMC.

2016


  • E. Allemand, M. P. Myers, J. Garcia-Bernardo, A. Harel-Bellan, A. R. Krainer, et C. Muchardt, « A Broad Set of Chromatin Factors Influences Splicing », PLoS genetics, vol. 12, nᵒ 9, p. e1006318, 2016.
    Résumé : Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and how direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset of chromatin-proteins, including histones and remodeling complexes like SWI/SNF. Yet, an unbiased RNAi screen revealed that the outcome of splicing is influenced by a much larger variety of chromatin factors not all associating with the spliceosome. The availability of this broad range of chromatin factors impacting splicing further unveiled their very context specific effect, resulting in either inclusion or skipping, depending on the exon under scrutiny. Finally, a direct assessment of the impact of chromatin on splicing using an in vitro co-transcriptional splicing assay with pre-mRNAs transcribed from a nucleosomal template, demonstrated that chromatin impacts nascent pre-mRNP in their competence for splicing. Altogether, our data show that numerous chromatin factors associated or not with the spliceosome can affect the outcome of splicing, possibly as a function of the local chromatin environment that by default interferes with the efficiency of splicing.
    Mots-clés : DBG, LEC.


  • S. Bakari, M. Lembrouk, L. Sourd, F. Ousalem, F. André, S. Orlowski, M. Delaforge, et A. Frelet-Barrand, « Lactococcus lactis is an Efficient Expression System for Mammalian Membrane Proteins Involved in Liver Detoxification, CYP3A4, and MGST1 », Molecular Biotechnology, vol. 58, nᵒ 4, p. 299-310, 2016.
    Mots-clés : B3S, DBG, LSOD, PEPS.

  • R. Balbontín, N. Villagra, M. Pardos de la Gándara, G. Mora, N. Figueroa-Bossi, et L. Bossi, « Expression of IroN, the salmochelin siderophore receptor, requires mRNA activation by RyhB small RNA homologues », Molecular Microbiology, vol. 100, nᵒ 1, p. 139-155, 2016.
    Résumé : The iroN gene of Salmonella enterica and uropathogenic Escherichia coli encodes the outer membrane receptor of Fe(3+) -bound salmochelin, a siderophore tailored to evade capture by the host's immune system. The iroN gene is under negative control of the Fur repressor and transcribed under iron limiting conditions. We show here that transcriptional de-repression is not sufficient to allow iroN expression, as this also requires activation by either of two partially homologous small RNAs (sRNAs), RyhB1 and RyhB2. The two sRNAs target the same sequence segment approximately in the middle of the 94-nucleotide 5' untranslated region (UTR) of iroN mRNA. Several lines of evidence suggest that base pair interaction stimulates iroN mRNA translation. Activation does not result from the disruption of a secondary structure masking the ribosome binding site; rather it involves sequences at the 5' end of iroN 5' UTR. In vitro 'toeprint' assays revealed that this upstream site binds the 30S ribosomal subunit provided that RyhB1 is paired with the mRNA. Altogether, our data suggest that RyhB1, and to lesser extent RyhB2, activate iroN mRNA translation by promoting entry of the ribosome at an upstream 'standby' site. These findings add yet an additional nuance to the polychromatic landscape of sRNA-mediated regulation.
    Mots-clés : 5' Untranslated Regions, Bacterial Outer Membrane Proteins, Bacterial Proteins, Base Sequence, Binding Sites, Codon, Initiator, Conserved Sequence, DBG, Gene Expression Regulation, Bacterial, Nucleic Acid Conformation, Nucleotide Motifs, Protein Binding, Receptors, Cell Surface, RGSP, Ribosomes, RNA Stability, RNA, Bacterial, RNA, Messenger, RNA-Binding Proteins.

  • E. Barbier, A. Lagorce, A. Hachemi, M. Dutertre, A. Gorlas, L. Morand, C. Saint-Pierre, J. - L. Ravanat, T. Douki, J. Armengaud, D. Gasparutto, F. Confalonieri, et J. Breton, « Oxidative DNA Damage and Repair in the Radioresistant Archaeon Thermococcus gammatolerans », Chemical Research in Toxicology, vol. 29, nᵒ 11, p. 1796-1809, 2016.
    Résumé : The hyperthermophilic archaeon Thermococcus gammatolerans can resist huge doses of γ-irradiation, up to 5.0 kGy, without loss of viability. The potential to withstand such harsh conditions is probably due to complementary passive and active mechanisms, including repair of damaged chromosomes. In this work, we documented the formation and repair of oxidative DNA lesions in T. gammatolerans. The basal level of the oxidized nucleoside, 8-oxo-2'-deoxyguanosine (8-oxo-dGuo), was established at 9.2 (± 0.9) 8-oxo-dGuo per 10(6) nucleosides, a higher level than those usually measured in eukaryotic cells or bacteria. A significant increase in oxidative damage, i.e., up to 24.2 (± 8.0) 8-oxo-dGuo/10(6) nucleosides, was measured for T. gammatolerans exposed to a 5.0 kGy dose of γ-rays. Surprisingly, the yield of radiation-induced modifications was lower than those previously observed for human cells exposed to doses corresponding to a few grays. One hour after irradiation, 8-oxo-dGuo levels were significantly reduced, indicating an efficient repair. Two putative base excision repair (BER) enzymes, TGAM_1277 and TGAM_1653, were demonstrated both by proteomics and transcriptomics to be present in the cells without exposure to ionizing radiation. Their transcripts were moderately upregulated after gamma irradiation. After heterologous production and purification of these enzymes, biochemical assays based on electrophoresis and MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectrometry indicated that both have a β-elimination cleavage activity. TGAM_1653 repairs 8-oxo-dGuo, whereas TGAM_1277 is also able to remove lesions affecting pyrimidines (1-[2-deoxy-β-d-erythro-pentofuranosyl]-5-hydroxyhydantoin (5-OH-dHyd) and 1-[2-deoxy-β-d-erythro-pentofuranosyl]-5-hydroxy-5-methylhydantoin (5-OH-5-Me-dHyd)). This work showed that in normal growth conditions or in the presence of a strong oxidative stress, T. gammatolerans has the potential to rapidly reduce the extent of DNA oxidation, with at least these two BER enzymes as bodyguards with distinct substrate ranges.
    Mots-clés : DBG, RBA.

  • A. Baudin-Baillieu, I. Hatin, R. Legendre, et O. Namy, « Translation Analysis at the Genome Scale by Ribosome Profiling », Methods in Molecular Biology (Clifton, N.J.), vol. 1361, p. 105-124, 2016.
    Résumé : Ribosome profiling is an emerging approach using deep sequencing of the mRNA part protected by the ribosome to study protein synthesis at the genome scale. This approach provides new insights into gene regulation at the translational level. In this review we describe the protocol to prepare polysomes and extract ribosome protected fragments before to deep sequence them.
    Mots-clés : DBG, Genome, GST, High-Throughput Nucleotide Sequencing, Polyribosomes, Protein Biosynthesis, Recoding, Ribo-seq, ribosome profiling, Ribosomes, RNA, Messenger, Translation regulation.

  • M. Blondel, F. Soubigou, J. Evrard, P. H. Nguyen, N. Hasin, S. Chédin, R. Gillet, M. - A. Contesse, G. Friocourt, G. Stahl, G. W. Jones, et C. Voisset, « Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation », Scientific Reports, vol. 6, p. 32117, 2016.
    Résumé : 6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI(+)] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases.
    Mots-clés : DBG, PEPS.

  • K. Bomblies, G. Jones, C. Franklin, D. Zickler, et N. Kleckner, « The challenge of evolving stable polyploidy: could an increase in "crossover interference distance" play a central role? », Chromosoma, vol. 125, nᵒ 2, p. 287-300, 2016.
    Résumé : Whole genome duplication is a prominent feature of many highly evolved organisms, especially plants. When duplications occur within species, they yield genomes comprising multiple identical or very similar copies of each chromosome ("autopolyploids"). Such genomes face special challenges during meiosis, the specialized cellular program that underlies gamete formation for sexual reproduction. Comparisons between newly formed (neo)-autotetraploids and fully evolved autotetraploids suggest that these challenges are solved by specific restrictions on the positions of crossover recombination events and, thus, the positions of chiasmata, which govern the segregation of homologs at the first meiotic division. We propose that a critical feature in the evolution of these more effective chiasma patterns is an increase in the effective distance of meiotic crossover interference, which plays a central role in crossover positioning. We discuss the findings in several organisms, including the recent identification of relevant genes in Arabidopsis arenosa, that support this hypothesis.
    Mots-clés : Chiasmata, Chromosomes, Plant, Crossing Over, Genetic, Crossover interference, DBG, DSMC, Evolution, Molecular, Homologous chromosomes, Meiosis, Plants, Polyploidy, Recombination.

  • L. Bossi et N. Figueroa-Bossi, « Competing endogenous RNAs: a target-centric view of small RNA regulation in bacteria », Nature Reviews. Microbiology, vol. 14, nᵒ 12, p. 775-784, 2016.
    Résumé : Many bacterial regulatory small RNAs (sRNAs) have several mRNA targets, which places them at the centre of regulatory networks that help bacteria to adapt to environmental changes. However, different mRNA targets of any given sRNA compete with each other for binding to the sRNA; thus, depending on relative abundances and sRNA affinity, competition for regulatory sRNAs can mediate cross-regulation between bacterial mRNAs. This 'target-centric' perspective of sRNA regulation is reminiscent of the competing endogenous RNA (ceRNA) hypothesis, which posits that competition for a limited pool of microRNAs (miRNAs) in higher eukaryotes mediates cross-regulation of mRNAs. In this Opinion article, we discuss evidence that a similar network of RNA crosstalk operates in bacteria, and that this network also includes crosstalk between sRNAs and competition for RNA-binding proteins.
    Mots-clés : DBG, RGSP.

  • P. Bouloc et F. Repoila, « Fresh layers of RNA-mediated regulation in Gram-positive bacteria », Current Opinion in Microbiology, vol. 30, p. 30-35, 2016.
    Résumé : Bacterial regulatory RNAs have been defined as diverse classes of cis and trans elements that may intervene at each step of gene expression, from RNA and protein synthesis to degradation. Here, we report on a few examples from Gram-positive bacteria that extend the definition of regulatory RNAs to include 5' and 3' UTRs that also act as cis and trans regulators. New examples unveil the existence of cis and trans acting regulatory RNAs on a single molecule. Also, we highlight data showing that a key RNA chaperone in Enterobacteriaceae, Hfq, does not fulfill the same role in Gram-positive Firmicutes.
    Mots-clés : Bacterial Proteins, DBG, Gene Expression Regulation, Bacterial, Gram-Positive Bacteria, RNA, Bacterial, SRRB.


  • A. Breiman, S. Fieulaine, T. Meinnel, et C. Giglione, « The intriguing realm of protein biogenesis: Facing the green co-translational protein maturation networks », Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, vol. 1864, nᵒ 5, p. 531-550, 2016.
    Mots-clés : B3S, Co-translational folding, Co-translational modifications, Co-translational targeting, DBG, IMAPP, Macromolecular Substances, Plants, PROMTI, Protein Biosynthesis, Protein Folding, Protein Processing, Post-Translational, Proteolysis, Ribosome, Ribosome-associated protein biogenesis factors, Ribosomes.

  • P. Brézellec, I. Vallet-Gely, C. Possoz, S. Quevillon-Cheruel, et J. - L. Ferat, « DciA is an ancestral replicative helicase operator essential for bacterial replication initiation », Nature Communications, vol. 7, p. 13271, 2016.
    Résumé : Delivery of the replicative helicase onto DNA is an essential step in the initiation of replication. In bacteria, DnaC (in Escherichia coli) and DnaI (in Bacillus subtilis) are representative of the two known mechanisms that assist the replicative helicase at this stage. Here, we establish that these two strategies cannot be regarded as prototypical of the bacterial domain since dnaC and dnaI (dna[CI]) are present in only a few bacterial phyla. We show that dna[CI] was domesticated at least seven times through evolution in bacteria and at the expense of one gene, which we rename dciA (dna[CI] antecedent), suggesting that DciA and Dna[CI] share a common function. We validate this hypothesis by establishing in Pseudomonas aeruginosa that DciA possesses the attributes of the replicative helicase-operating proteins associated with replication initiation.
    Mots-clés : DBG, EMC2, OCB.

  • M. Costa, H. Walbott, D. Monachello, E. Westhof, et F. Michel, « Crystal structures of a group II intron lariat primed for reverse splicing », Science (New York, N.Y.), vol. 354, nᵒ 6316, 2016.
    Résumé : The 2'-5' branch of nuclear premessenger introns is believed to have been inherited from self-splicing group II introns, which are retrotransposons of bacterial origin. Our crystal structures at 3.4 and 3.5 angstrom of an excised group II intron in branched ("lariat") form show that the 2'-5' branch organizes a network of active-site tertiary interactions that position the intron terminal 3'-hydroxyl group into a configuration poised to initiate reverse splicing, the first step in retrotransposition. Moreover, the branchpoint and flanking helices must undergo a base-pairing switch after branch formation. A group II-based model of the active site of the nuclear splicing machinery (the spliceosome) is proposed. The crucial role of the lariat conformation in active-site assembly and catalysis explains its prevalence in modern splicing.
    Mots-clés : DBG, RIBOZYMO, RNASTR.

  • R. Culerrier, M. Carraz, C. Mann, et M. Djabali, « MSK1 triggers the expression of the INK4AB/ARF locus in oncogene-induced senescence », Molecular Biology of the Cell, vol. 27, nᵒ 17, p. 2726-2734, 2016.
    Résumé : The tumor suppressor proteins p15(INK4B), p16(INK4A), and p14(ARF), encoded by the INK4AB/ARF locus, are crucial regulators of cellular senescence. The locus is epigenetically silenced by the repressive Polycomb complexes in growing cells but is activated in response to oncogenic stress. Here we show that the mitogen- and stress-activated kinase (MSK1) is up-regulated after RAF1 oncogenic stress and that the phosphorylated (activated) form of MSK1 is significantly increased in the nucleus and recruited to the INK4AB/ARF locus. We show that MSK1 mediates histone H3S28 phosphorylation at the INK4AB/ARF locus and contributes to the rapid transcriptional activation of p15(INK4B) and p16(INK4A) in human cells despite the presence of the repressive H3K27me3 mark. Furthermore, we show that upon MSK1 depletion in oncogenic RAF1-expressing cells, H3S28ph presence at the INK4 locus and p15(INK4B) and p16(INK4A) expression are reduced. Finally, we show that H3S28-MSK-dependent phosphorylation functions in response to RAF1 signaling and that ERK and p38α contribute to MSK1 activation in oncogene-induced senescence.
    Mots-clés : DBG, SEN.

  • M. de Dieuleveult, K. Yen, I. Hmitou, A. Depaux, F. Boussouar, D. Bou Dargham, S. Jounier, H. Humbertclaude, F. Ribierre, C. Baulard, N. P. Farrell, B. Park, C. Keime, L. Carrière, S. Berlivet, M. Gut, I. Gut, M. Werner, J. - F. Deleuze, R. Olaso, J. - C. Aude, S. Chantalat, B. F. Pugh, et M. Gérard, « Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells », Nature, vol. 530, nᵒ 7588, p. 113-116, 2016.
    Résumé : ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.
    Mots-clés : Animals, Chromatin Assembly and Disassembly, DBG, DNA Helicases, DNA-Binding Proteins, Gene Expression Regulation, Genome, GTR, Histones, Mice, Micrococcal Nuclease, Mouse Embryonic Stem Cells, Nuclear Proteins, Nucleosomes, Promoter Regions, Genetic, REMOD, RNA Polymerase II, Substrate Specificity, Trans-Activators, Transcription Factors, Transcription Initiation Site.


  • E. Deforzh, T. Vargas, J. Kropp, M. Vandamme, G. Pinna, et A. Polesskaya, « IMP-3 protects the mRNAs of cyclins D1 and D3 from GW182/AGO2-dependent translational repression », International Journal of Oncology, oct. 2016.
    Mots-clés : DBG, PARI, PF, RPTEG.

  • C. Denby Wilkes, O. Arnaiz, et L. Sperling, « ParTIES: a toolbox for Paramecium interspersed DNA elimination studies », Bioinformatics (Oxford, England), vol. 32, nᵒ 4, p. 599-601, 2016.
    Résumé : MOTIVATION: Developmental DNA elimination occurs in a wide variety of multicellular organisms, but ciliates are the only single-celled eukaryotes in which this phenomenon has been reported. Despite considerable interest in ciliates as models for DNA elimination, no standard methods for identification and characterization of the eliminated sequences are currently available. RESULTS: We present the Paramecium Toolbox for Interspersed DNA Elimination Studies (ParTIES), designed for Paramecium species, that (i) identifies eliminated sequences, (ii) measures their presence in a sequencing sample and (iii) detects rare elimination polymorphisms. AVAILABILITY AND IMPLEMENTATION: ParTIES is multi-threaded Perl software available at https://github.com/oarnaiz/ParTIES. ParTIES is distributed under the GNU General Public Licence v3.
    Mots-clés : ANGE, Ciliophora Infections, DBG, DNA, Protozoan, Genome, Protozoan, Interspersed Repetitive Sequences, Paramecium, Protozoan Proteins, Software.

  • Y. Deng, C. Chen, Z. Zhao, J. Zhao, A. Jacq, X. Huang, et Y. Yang, « The RNA Chaperone Hfq Is Involved in Colony Morphology, Nutrient Utilization and Oxidative and Envelope Stress Response in Vibrio alginolyticus », PloS One, vol. 11, nᵒ 9, p. e0163689, 2016.
    Résumé : Hfq is a global regulator that is involved in environmental adaptation of bacteria and in pathogenicity. To gain insight into the role of Hfq in Vibrio alginolyticus, an hfq deletion mutant was constructed in V. alginolyticus ZJ-T strain and phenotypically characterized. Deletion of hfq led to an alteration of colony morphology and reduced extracellular polysaccharide production, a general impairment of growth in both rich medium and minimal media with different carbon sources or amino acids, enhanced sensitivity to oxidative stress and to several antibiotics. Furthermore, a differential transcriptomic analysis showed significant changes of transcript abundance for 306 protein coding genes, with 179 genes being up regulated and 127 down-regulated. Several of these changes could be related to the observed phenotypes of the mutant. Transcriptomic data also provided evidence for the induction of the extracytoplasmic stress response in absence of Hfq. Altogether, these findings point to broad regulatory functions for Hfq in V. alginolyticus cells, likely to underlie an important role in pathogenicity.
    Mots-clés : DBG, SRRB.

  • A. Devigne, P. Guérin, J. Lisboa, S. Quevillon-Cheruel, J. Armengaud, S. Sommer, C. Bouthier de la Tour, et P. Servant, « PprA Protein Is Involved in Chromosome Segregation via Its Physical and Functional Interaction with DNA Gyrase in Irradiated Deinococcus radiodurans Bacteria », mSphere, vol. 1, nᵒ 1, 2016.
    Résumé : PprA, a radiation-induced Deinococcus-specific protein, was previously shown to be required for cell survival and accurate chromosome segregation after exposure to ionizing radiation. Here, we used an in vivo approach to determine, by shotgun proteomics, putative PprA partners coimmunoprecipitating with PprA when cells were exposed to gamma rays. Among them, we found the two subunits of DNA gyrase and, thus, chose to focus our work on characterizing the activities of the deinococcal DNA gyrase in the presence or absence of PprA. Loss of PprA rendered cells hypersensitive to novobiocin, an inhibitor of the B subunit of DNA gyrase. We showed that treatment of bacteria with novobiocin resulted in induction of the radiation desiccation response (RDR) regulon and in defects in chromosome segregation that were aggravated by the absence of PprA. In vitro, the deinococcal DNA gyrase, like other bacterial DNA gyrases, possesses DNA negative supercoiling and decatenation activities. These two activities are inhibited in vitro by novobiocin and nalidixic acid, whereas PprA specifically stimulates the decatenation activity of DNA gyrase. Together, these results suggest that PprA plays a major role in chromosome decatenation via its interaction with the deinococcal DNA gyrase when D. radiodurans cells are recovering from exposure to ionizing radiation. IMPORTANCE D. radiodurans is one of the most radiation-resistant organisms known. This bacterium is able to cope with high levels of DNA lesions generated by exposure to extreme doses of ionizing radiation and to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Here, we identified partners of PprA, a radiation-induced Deinococcus-specific protein, previously shown to be required for radioresistance. Our study leads to three main findings: (i) PprA interacts with DNA gyrase after irradiation, (ii) treatment of cells with novobiocin results in defects in chromosome segregation that are aggravated by the absence of PprA, and (iii) PprA stimulates the decatenation activity of DNA gyrase. Our results extend the knowledge of how D. radiodurans cells survive exposure to extreme doses of gamma irradiation and point out the link between DNA repair, chromosome segregation, and DNA gyrase activities in the radioresistant D. radiodurans bacterium.
    Mots-clés : DBG, Deinococcus radiodurans, DNA decatenation, DNA gyrase, PprA, RBA.

  • E. L. Dubois, S. Gerber, A. Kisselev, A. Harel-Bellan, et R. Groisman, « UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis », Oncology Reports, vol. 35, nᵒ 5, p. 3101-3105, 2016.
    Résumé : The COP9/signalosome (CSN) multi-protein complex regulates the activity of cullin-RING ubiquitin ligases (CRLs), including the DDB2 and CSA CRL4 ligases (CRL4DDB2 and CRL4CSA), which are involved in the repair of UV-induced DNA damages. In the present study, we demonstrated that the protein kinase ATM, a key component of the DNA damage response (DDR), phosphorylates CSN1 and CSN7a, two subunits of the CSN complex, in a UV-dependent manner. The phosphorylation of CSN1 on serine 474 was detected as early as 3 h after UV-exposure, peaked at 8 h and persisted until 48 h post-UV irradiation. Such a time course suggests a role in late DDR rather than in DNA repair. Consistently, overexpression of a phosphorylation-resistant S474A CSN1 mutant reduced UV-induced apoptosis. Thus, CSN1 appears to play a role not only in DNA repair but also in UV-induced apoptosis.
    Mots-clés : Apoptosis, Ataxia Telangiectasia Mutated Proteins, DBG, DNA Damage, DNA Repair, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, LEC, Multiprotein Complexes, Peptide Hydrolases, Phosphorylation, Protein Processing, Post-Translational, Ultraviolet Rays.

  • A. Durand, A. K. Sinha, C. Dard-Dascot, et B. Michel, « Mutations Affecting Potassium Import Restore the Viability of the Escherichia coli DNA Polymerase III holD Mutant », PLoS genetics, vol. 12, nᵒ 6, p. e1006114, 2016.
    Résumé : Mutants lacking the ψ (HolD) subunit of the Escherichia coli DNA Polymerase III holoenzyme (Pol III HE) have poor viability, but a residual growth allows the isolation of spontaneous suppressor mutations that restore ΔholD mutant viability. Here we describe the isolation and characterization of two suppressor mutations in the trkA and trkE genes, involved in the main E. coli potassium import system. Viability of ΔholD trk mutants is abolished on media with low or high K+ concentrations, where alternative K+ import systems are activated, and is restored on low K+ concentrations by the inactivation of the alternative Kdp system. These findings show that the ΔholD mutant is rescued by a decrease in K+ import. The effect of trk inactivation is additive with the previously identified ΔholD suppressor mutation lexAind that blocks the SOS response indicating an SOS-independent mechanism of suppression. Accordingly, although lagging-strand synthesis is still perturbed in holD trkA mutants, the trkA mutation allows HolD-less Pol III HE to resist increased levels of the SOS-induced bypass polymerase DinB. trk inactivation is also partially additive with an ssb gene duplication, proposed to stabilize HolD-less Pol III HE by a modification of the single-stranded DNA binding protein (SSB) binding mode. We propose that lowering the intracellular K+ concentration stabilizes HolD-less Pol III HE on DNA by increasing electrostatic interactions between Pol III HE subunits, or between Pol III and DNA, directly or through a modification of the SSB binding mode; these three modes of action are not exclusive and could be additive. To our knowledge, the holD mutant provides the first example of an essential protein-DNA interaction that strongly depends on K+ import in vivo.
    Mots-clés : DBG, STABAC.

  • T. Eychenne, E. Novikova, M. - B. Barrault, O. Alibert, C. Boschiero, N. Peixeiro, D. Cornu, V. Redeker, L. Kuras, P. Nicolas, M. Werner, et J. Soutourina, « Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture », Genes & Development, vol. 30, nᵒ 18, p. 2119-2132, 2016.
    Résumé : Mediator is a large coregulator complex conserved from yeast to humans and involved in many human diseases, including cancers. Together with general transcription factors, it stimulates preinitiation complex (PIC) formation and activates RNA polymerase II (Pol II) transcription. In this study, we analyzed how Mediator acts in PIC assembly using in vivo, in vitro, and in silico approaches. We revealed an essential function of the Mediator middle module exerted through its Med10 subunit, implicating a key interaction between Mediator and TFIIB. We showed that this Mediator-TFIIB link has a global role on PIC assembly genome-wide. Moreover, the amplitude of Mediator's effect on PIC formation is gene-dependent and is related to the promoter architecture in terms of TATA elements, nucleosome occupancy, and dynamics. This study thus provides mechanistic insights into the coordinated function of Mediator and TFIIB in PIC assembly in different chromatin contexts.
    Mots-clés : DBG, GTR, Mediator, PEPS, PF, preinitiation complex, promoter architecture, RNA polymerase II transcription, Saccharomyces cerevisiae, SICAPS, TFIIB.


  • S. Fieulaine, R. Alves de Sousa, L. Maigre, K. Hamiche, M. Alimi, J. - M. Bolla, A. Taleb, A. Denis, J. - M. Pagès, I. Artaud, T. Meinnel, et C. Giglione, « A unique peptide deformylase platform to rationally design and challenge novel active compounds », Scientific Reports, vol. 6, p. 35429, oct. 2016.


  • F. Frottin, W. V. Bienvenut, J. Bignon, E. Jacquet, A. Sebastian Vaca Jacome, A. Van Dorsselaer, S. Cianferani, C. Carapito, T. Meinnel, et C. Giglione, « MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state », Oncotarget, sept. 2016.
    Mots-clés : Cotranslational modifications, DBG, glutathione redox homeostasis, Methionine aminopeptidase, N-terminal processing, PROMTI, quantitative targeted proteomics.

  • S. Galardi, M. Petretich, G. Pinna, S. D'Amico, F. Loreni, A. Michienzi, I. Groisman, et S. A. Ciafrè, « CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation », Scientific Reports, vol. 6, p. 25219, 2016.
    Résumé : The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3' untranslated regions (3'UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27(Kip1) by specifically targeting its 3'UTR, and competes with miR-221/222 binding at an overlapping site in the 3'UTR, thus impairing miR-221/222 inhibitory activity. Upon binding to p27(Kip1) 3'UTR, CPEB1 promotes elongation of poly-A tail and the subsequent translation of p27(Kip1) mRNA. This leads to higher levels of p27(Kip1) in the cell, in turn significantly inhibiting cell proliferation, and confers to CPEB1 a potential value as a tumor suppressor in Glioblastoma.
    Mots-clés : DBG, LEC.

  • A. R. Gall, K. A. Datsenko, N. Figueroa-Bossi, L. Bossi, I. Masuda, Y. - M. Hou, et L. N. Csonka, « Mg2+ regulates transcription of mgtA in Salmonella Typhimurium via translation of proline codons during synthesis of the MgtL peptide », Proceedings of the National Academy of Sciences of the United States of America, vol. 113, nᵒ 52, p. 15096-15101, 2016.
    Résumé : In Salmonella enterica serovar Typhimurium, Mg(2+) limitation induces transcription of the mgtA Mg(2+) transport gene, but the mechanism involved is unclear. The 5' leader of the mgtA mRNA contains a 17-codon, proline-rich ORF, mgtL, whose translation regulates the transcription of mgtA [Park S-Y et al. (2010) Cell 142:737-748]. Rapid translation of mgtL promotes formation of a secondary structure in the mgtA mRNA that permits termination of transcription by the Rho protein upstream of mgtA, whereas slow or incomplete translation of mgtL generates a different structure that blocks termination. We identified the following mutations that conferred high-level transcription of mgtA at high [Mg(2+)]: (i) a base-pair change that introduced an additional proline codon into mgtL, generating three consecutive proline codons; (ii) lesions in rpmA and rpmE, which encode ribosomal proteins L27 and L31, respectively; (iii) deletion of efp, which encodes elongation factor EF-P that assists the translation of proline codons; and (iv) a heat-sensitive mutation in trmD, whose product catalyzes the m(1)G37 methylation of tRNA(Pro) Furthermore, substitution of three of the four proline codons in mgtL rendered mgtA uninducible. We hypothesize that the proline codons present an impediment to the translation of mgtL, which can be alleviated by high [Mg(2+)] exerted on component(s) of the translation machinery, such as EF-P, TrmD, or a ribosomal factor. Inadequate [Mg(2+)] precludes this alleviation, making mgtL translation inefficient and thereby permitting mgtA transcription. These findings are a significant step toward defining the target of Mg(2+) in the regulation of mgtA transcription.
    Mots-clés : 50S ribosomal proteins, DBG, EF-P translation factor, MgtA Mg2+ transporter, MgtL leader peptide, RGSP, TrmD methyltransferase.


  • E. Galli, M. Poidevin, R. Le Bars, J. - M. Desfontaines, L. Muresan, E. Paly, Y. Yamaichi, et F. - X. Barre, « Cell division licensing in the multi-chromosomal Vibrio cholerae bacterium », Nature Microbiology, vol. 1, nᵒ 9, p. 16094, juin 2016.
    Mots-clés : DBG, EMC2, EQYY, PF, PHOT.

  • A. Goldar, A. Arneodo, B. Audit, F. Argoul, A. Rappailles, G. Guilbaud, N. Petryk, M. Kahli, et O. Hyrien, « Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations », Scientific Reports, vol. 6, p. 22469, 2016.
    Résumé : We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.
    Mots-clés : Cell Line, Chromatin, DBG, DNA Replication, GTR, Humans, Replication Origin, Saccharomyces cerevisiae.

  • H. Grosjean et E. Westhof, « An integrated, structure- and energy-based view of the genetic code », Nucleic Acids Research, vol. 44, nᵒ 17, p. 8020-8040, 2016.
    Résumé : The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson-Crick pairs in the codon-anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids.
    Mots-clés : DBG, RNASTR.

  • S. Hacquard, B. Kracher, K. Hiruma, P. C. Münch, R. Garrido-Oter, M. R. Thon, A. Weimann, U. Damm, J. - F. Dallery, M. Hainaut, B. Henrissat, O. Lespinet, S. Sacristán, E. V. L. van Themaat, E. Kemen, A. C. McHardy, P. Schulze-Lefert, et R. J. O'Connell, « Erratum: Survival trade-offs in plant roots during colonization by closely related beneficial and pathogenic fungi », Nature Communications, vol. 7, p. 13072, 2016.

  • S. Hacquard, B. Kracher, K. Hiruma, P. C. Münch, R. Garrido-Oter, M. R. Thon, A. Weimann, U. Damm, J. - F. Dallery, M. Hainaut, B. Henrissat, O. Lespinet, S. Sacristán, E. Ver Loren van Themaat, E. Kemen, A. C. McHardy, P. Schulze-Lefert, et R. J. O'Connell, « Survival trade-offs in plant roots during colonization by closely related beneficial and pathogenic fungi », Nature Communications, vol. 7, p. 11362, 2016.
    Résumé : The sessile nature of plants forced them to evolve mechanisms to prioritize their responses to simultaneous stresses, including colonization by microbes or nutrient starvation. Here, we compare the genomes of a beneficial root endophyte, Colletotrichum tofieldiae and its pathogenic relative C. incanum, and examine the transcriptomes of both fungi and their plant host Arabidopsis during phosphate starvation. Although the two species diverged only 8.8 million years ago and have similar gene arsenals, we identify genomic signatures indicative of an evolutionary transition from pathogenic to beneficial lifestyles, including a narrowed repertoire of secreted effector proteins, expanded families of chitin-binding and secondary metabolism-related proteins, and limited activation of pathogenicity-related genes in planta. We show that beneficial responses are prioritized in C. tofieldiae-colonized roots under phosphate-deficient conditions, whereas defense responses are activated under phosphate-sufficient conditions. These immune responses are retained in phosphate-starved roots colonized by pathogenic C. incanum, illustrating the ability of plants to maximize survival in response to conflicting stresses.
    Mots-clés : BIM, DBG.

  • D. Hamdane, H. Grosjean, et M. Fontecave, « Flavin-Dependent Methylation of RNAs: Complex Chemistry for a Simple Modification », Journal of Molecular Biology, vol. 428, nᵒ 24 Pt B, p. 4867-4881, 2016.
    Résumé : RNA methylation is the most abundant and evolutionarily conserved chemical modification of bases or ribose in noncoding and coding RNAs. This rather simple modification has nevertheless major consequences on the function of maturated RNA molecules and ultimately on their cellular fates. The methyl group employed in the methylation is almost universally derived from S-adenosyl-L-methionine via a simple SN2 displacement reaction. However, in some rare cases, the carbon originates from N5,N10-methylenetetrahydrofolate (CH2=THF). Here, a methylene group is transferred first and requires a subsequent reduction step (2e(-)+H(+)) via the flavin adenine dinucleotide hydroquinone (FADH(-)) to form the final methylated derivative. This FAD/folate-dependent mode of chemical reaction, called reductive methylation, is thus far more complex than the usual simple S-adenosyl-L-methionine-dependent one. This reaction is catalyzed by flavoenzymes, now named TrmFO and RlmFO, which respectively modify transfer and ribosomal RNAs. In this review, we briefly recount how these new RNA methyltransferases were discovered and describe a novel aspect of the chemistry of flavins, wherein this versatile biological cofactor is not just a simple redox catalyst but is also a new methyl transfer agent acting via a critical CH2=(N5)FAD iminium intermediate. The enigmatic structural reorganization of these enzymes that needs to take place during catalysis in order to build their active center is also discussed. Finally, recent findings demonstrated that this flavin-dependent mechanism is also employed by enzymatic systems involved in DNA synthesis, suggesting that the use of this cofactor as a methylating agent of biomolecules could be far more usual than initially anticipated.
    Mots-clés : 5-methyluridine, DBG, flavoenzyme, methylation mechanism, methyltransferase, RNA, RNASTR.

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