Papers by André Mazabraud
Research article Exploring nervous system transcriptomes during embryogenesis and metamorphosis i... more Research article Exploring nervous system transcriptomes during embryogenesis and metamorphosis in Xenopus tropicalis using EST analysis
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Santé (Montrouge, France)
A major endemic in Côte d'Ivoire, malaria is the first cause of hospital admissions and morta... more A major endemic in Côte d'Ivoire, malaria is the first cause of hospital admissions and mortality in tropical Africa. The decrease of morbidity and mortality depends on early diagnosis and relevant treatment. This situation is hampered by an emerging resistance of P. falciparum to usual drugs such as chloroquine and sulfadoxine-pyrimethamine. In recognition of this problem, we established a monitoring system in the north of Abidjan (Yopougon) in order to better analyse P. falciparum resistance. The molecular basis of P. falciparum resistance to pyrimethamine is associated with point mutations in the dihydrofolate reductase (dhfr) gene. The presence of a wild-type codon 108-ser is defined by the presence of an Alu1 restriction site. A single base change resulting in the change of amino acid from 108-Ser to 108-Asn or 108-Thr results in the appearance of a Bsr1 or a Scrf1 restriction site respectively. In response to these needs, 42 children aged 6 to 59 months were enrolled in th...
Journal of Molecular Biology, 1987
Termination of RNA polymerase III transcripts commonly occurs at clusters of T residues. A T4 tra... more Termination of RNA polymerase III transcripts commonly occurs at clusters of T residues. A T4 tract located 72 base-pairs beyond a lysine tRNA gene from Xenopus lawis serves as an efficient termination site for the tRNALys precursors synthesized from this gene in homologous cell-free extracts. Nucleotides following this T tract influence the extent of read-through transcription in vitro, but in a way that differs from Xenopus 5 S RNA termination. Only w 50 7& of the transcripts initiated in vitro extend as far as this downstream T cluster. The remainder prematurely terminate at a second T4 tract located within the gene itself. The contrasting behaviour of these two T tracts in injected oocytes indicates that termination can be influenced by more than just RNA polymerase III alone, and that different components may contribute to, or hinder, termination at these sites. Prematurely terminated tRNA Lys transcripts are detectable in RNA from ovary tissue but not from a kidney cell line, suggesting that read-through transcription beyond intragenic T clusters can be modulated in viva.
Developmental Dynamics, 2007
We analyzed the effects of Rho GTPases on XSnail2 expression during neural crest (NC) ontogeny in... more We analyzed the effects of Rho GTPases on XSnail2 expression during neural crest (NC) ontogeny in Xenopus laevis embryos. The ectopic expression of both dominant-negative (N-) and constitutively active (V-) Rho GTPase mutants after RNA or DNA microinjection disrupted the endogenous expression of XSnail2, XFoxD3, and XSnail1. V14RhoA and N17Rac1 were inhibitory, whereas N19RhoA and V12Rac1 increased NC marker gene expression. In reporter assays using a XSnail2 promoter-green fluorescent protein (GFP) construct (alpha700BA-GFP), the ectopic expression of V14RhoA, N17Rac1, or the Rac1 inhibitor NSC 23766 decreased reporter expression in NC-neural plate, whereas N19RhoA or the RhoA inhibitor Y27632 and V12Rac1 enhanced it. Similarly, transgenic embryos expressing Rho GTPase mutants and GFP under control of the alpha700BA promoter displayed variations similar to those observed for ectopic RNA and DNA expression. These results show that Rho GTPases can regulate the expression of XSnail2 during NC ontogeny.
Biology of the Cell, 1996
We have shown the presence of at least two genes specifying the nucleoside diphosphate kinase (ND... more We have shown the presence of at least two genes specifying the nucleoside diphosphate kinase (NDPK or NM23, metastasis suppressor) in the toad Xenopus laevis, as in mammals. Gel retardation assays showed that enzyme Xl, but not X3, binds to pyrimidine-rich regions of nucleic acids, such as "CT" repeats. It also recognizes the "CCCACCC" motif of the human c-myc promoter, just like the human NDPK B, characterized as the PUF19 transcription activator factor (Postel E.H., et n1.(1996), Proc. Natl. Acad. Sci.,93,6892-6897). This motif is also found in the first exon of c-myc and ki-ras Xenopus genes, as well as in the 3' noncoding sequence of Xenopus NDPK mRNA, suggesting a self post-transcriptional regulation of the different isozymes. During embryonic development, NDPK is heterogeneously distributed, being abundant in rapidly dividing cells and in the nuclei of migrating embryonic cells. In toto hybridization with anti-mRNA revealed isozyme mRNA specific patterns during somite formation. Immunodetection of NDPK in Xenopus 693N immortalised cells and T30-derived invasive cells detected a single isoform migrating as the NDPK Xl hexamer in T30. These results indicate that there may be functional differences between the two NDPK. We have also tested the capacity of Xenopus NDPK to rescue mutant Drosophila aw& larvae lacking NDPK. Xenopus NDPK Xl-X3 rescues these larvae, but the fertility of the resulting females was not restored. Presently, we are investigating the functions of the CCCACCC motif in stabilisation, polyadenylation or translation.of NDPK Xenopus mRNA and in the expression of c-myc and ki-ras Xenopus genes, both in vitro and in vivo. Our preliminary results suggest that NDPK Xl is able to bind to its own mRNA and stabilise it in a S 100 Xenopus oocyte extract.
FEMS Microbiology Letters, 2006
Sulpha drugs act as competitive inhibitors of p-amino benzoic acid, an intermediate in the de nov... more Sulpha drugs act as competitive inhibitors of p-amino benzoic acid, an intermediate in the de novo folate pathway. Dihydropteroate synthase condenses sulpha drugs into sulpha-dihydropteroate (sulpha-DHP), which competes with dihydrofolate, the dihydrofolate reductase (DHFR) substrate. This designates DHFR as a possible target of sulpha-DHP. We suggest here that Plasmodium vivax DHFR is indeed the in vivo target of sulpha drugs. The wild-type DHFR expressed in Saccharomyces cerevisiae leads to cell growth inhibition, while sensitivity to the drug is exacerbated in the mutants. Contrary to what is observed with sulphanilamide, methotrexate is less effective on P. vivax-DHFR mutants than on wild-type mutant.
Fréquence du polymorphisme C677T du gène de la méthylène tetrahydrofolate réductase (MTHFR) dans ... more Fréquence du polymorphisme C677T du gène de la méthylène tetrahydrofolate réductase (MTHFR) dans les populations arabe et berbère du Maroc Frequency of C677T polymorphism of methylene tetrahyrofolate reductase (MTHFR) gene among berber and arabic Moroccan populations
Http Www Theses Fr, 1993
Nous avons etudie l'expression des genes specifiant plusieurs elements du systeme de synthese... more Nous avons etudie l'expression des genes specifiant plusieurs elements du systeme de synthese proteique pendant la gametogenese et l'embryogenese de xenopus laevis. Les genes etudies sont ceux qui codent pour le facteur d'elongation 1 alpha (ef-1 alpha), la thesaurine a et la thesaurine b. Ces deux dernieres proteines sont impliquees dans le stockage a long terme du rna 5s et du trna dans les oocytes. Elles ne sont pas detectables dans les cellules somatiques. Ef-1 alpha existe sous deux formes: une forme somatique (ef-1 alphas) et une forme oocytaire (ef-1 alphao). On demontre ici que le rna messager de ef-1 alphas est indetectable dans les oocytes et les spermatocytes, mais qu'il est present dans les cellules embryonnaires a partir du stade neurula. Le rna messager de ef-1 alphao est present non seulement dans les oogonies et les oocytes de tous les stades, mais aussi dans les spermatogonies et les spermatocytes primaires. Les rna messagers codant pour la thesaurine a et la thesaurine b sont egalement specifiques des cellules germinales. Ils sont traduits en proteines dans le testicule comme ils le sont dans l'ovaire. Cette etude revele une similitude frappante dans le programme d'expression des genes durant l'oogenese et la spermatogenese. Les produits des genes ef-1 alphao, thesaurine a et la thesaurine b peuvent etre consideres comme des marqueurs de la differenciation des cellules germinales
neurogenetics, 2010
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss a... more Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy. The loss of function of the smn1 gene, the main supplier of survival motor neuron protein (SMN) protein in human, leads to reduced levels of SMN and eventually to SMA. Here, we ask if the amphibian Xenopus tropicalis can be a good model system to study SMA. Inhibition of the production of SMN using antisense morpholinos leads to caudal muscular atrophy in tadpoles. Of note, early developmental patterning of muscles and motor neurons is unaffected in this system as well as acetylcholine receptors clustering. Muscular atrophy seems to rather result from aberrant pathfinding and growth arrest and/or shortening of motor axons. This event occurs in the absence of neuronal cell bodies apoptosis, a process comparable to that of amyotrophic lateral sclerosis. Xenopus tropicalis is revealed as a complementary animal model for the study of SMA.
neurogenetics, 2010
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss a... more Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy. The loss of function of the smn1 gene, the main supplier of survival motor neuron protein (SMN) protein in human, leads to reduced levels of SMN and eventually to SMA. Here, we ask if the amphibian Xenopus tropicalis can be a good model system to study SMA. Inhibition of the production of SMN using antisense morpholinos leads to caudal muscular atrophy in tadpoles. Of note, early developmental patterning of muscles and motor neurons is unaffected in this system as well as acetylcholine receptors clustering. Muscular atrophy seems to rather result from aberrant pathfinding and growth arrest and/or shortening of motor axons. This event occurs in the absence of neuronal cell bodies apoptosis, a process comparable to that of amyotrophic lateral sclerosis. Xenopus tropicalis is revealed as a complementary animal model for the study of SMA.
Experimental Parasitology, 1998
Biogerontology
eEF1A is encoded by a unique gene in the filamentous fungus Podospora anserina. We show here that... more eEF1A is encoded by a unique gene in the filamentous fungus Podospora anserina. We show here that (1) this gene is essential for vegetative growth, (2) readthrough at UGA stop codon level is positively correlated with eEF1A level, (3) eEF1A level is regulated in P. anserina. (4) Increasing eEF1A gene dosage does not modify P. anserina life cycle parameters, especially longevity is not changed. These data confirm and extend those previously obtained in yeast and Drosophila.
Journal of Biological Chemistry
Thesaurin a is one of two protein components of a 42 S ribonucleoprotein particle that is very ab... more Thesaurin a is one of two protein components of a 42 S ribonucleoprotein particle that is very abundant in previtellogenic oocytes of Xenopus laevis. The primary function of the 42 S particle is the long-term storage of 5 S RNA and aminoacyl-tRNA. Thesaurin a is homologous to eukaryotic elongation factor 1 alpha (EF-1 alpha) and to prokaryotic elongation factor Tu (EF-Tu). Sequence comparison with EF-1 alpha and EF-Tu of different species indicates that thesaurin a is rather distantly related to all eukaryotic elongation factors. In spite of this, the secondary structure of thesaurin a, deduced from hydrophobic cluster analysis, is remarkably similar to that of EF-1 alpha and EF-Tu. The binding and catalytic properties of thesaurin a are also similar but not identical to those of EF-1 alpha. Like EF-1 alpha, purified thesaurin a binds tRNA, GDP, and GTP. Unlike EF-1 alpha, thesaurin a binds discharged tRNA more tightly than charged tRNA, and GTP more tightly than GDP. Thesaurin a al...
Development
As components of the 42S storage particles (thesaurisomes), thesaurin a and thesaurin b are invol... more As components of the 42S storage particles (thesaurisomes), thesaurin a and thesaurin b are involved in the long-term storage of tRNA and 5S RNA in previtellogenic oocytes of Xenopus laevis. Thesaurin a and thesaurin b are among the most abundant proteins in previtellogenic oocytes. We show here that the mRNAs encoding thesaurin a and thesaurin b are present not only in previtellogenic oocytes but also in pre-meiotic germ cells (oogonia). These mRNAs can also be detected in spermatogonia and early spermatocytes, and are translated into protein in testis, as they are in ovary. We conclude that male germ cells mimic female germ cells in several aspects of gene activity related to RNA accumulation and metabolism.
Biogerontology, 2000
eEF1A is encoded by a unique gene in the filamentous fungus Podospora anserina. We show here that... more eEF1A is encoded by a unique gene in the filamentous fungus Podospora anserina. We show here that (1) this gene is essential for vegetative growth, (2) readthrough at UGA stop codon level is positively correlated with eEF1A level, (3) eEF1A level is regulated in P. anserina. (4) Increasing eEF1A gene dosage does not modify P. anserina life cycle parameters, especially longevity is not changed. These data confirm and extend those previously obtained in yeast and Drosophila.
Molecular and biochemical parasitology, 1998
The gene encoding dihydrofolate reductase-thymidylate synthase of the human malaria parasite, Pla... more The gene encoding dihydrofolate reductase-thymidylate synthase of the human malaria parasite, Plasmodium vivax, was isolated by polymerase chain reaction from genomic DNA and cloned. The sequences of the dihydrofolate reductase domain of 30 clinical isolates originating from various geographic areas were compared. Interstrain analysis revealed several genotypic variations, including short tandem repeat arrays which produced length polymorphism between different parasite isolates and point mutations in the putative dihydrofolate reductase active site cavity corresponding to those associated with pyrimethamine resistance in P. falciparum and rodent malaria parasites. Amino acid substitutions Ser-->Asn-117 and Ser-->Arg-58 were associated with decreased level of in vitro pyrimethamine sensitivity. These findings suggest that the P. vivax dihydrofolate reductase domain is characterized by polymorphism that has not been observed in P. falciparum and may explain the resistance of so...
European Journal of Biochemistry, 1975
The nucleotide sequence of initiator tRNA, tRNAfMet, from vitellogenic oocytes of Xenopus laevis ... more The nucleotide sequence of initiator tRNA, tRNAfMet, from vitellogenic oocytes of Xenopus laevis was determined. The sequence was deduced from analysis of all T1 and pancreatic oligonucleotides and comparison with the sequence of initiator tRNA from other animal species. At least 80% of all initiator tRNA molecules from oocytes have the same nucleotide sequence. This means that most and probably all initiator tRNA genes which are active in oocytes are identical to one another. No structural difference was observed between liver and oocyte initiator tRNAs. Initiator tRNA from X. laevis has the same nucleotide sequence as initiator tRNA from several species of mammals. The genes coding for this RNA have therefore remained unchanged in the mammalian and amphibian lines for at least 300000000 years.
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Papers by André Mazabraud