Jason S Iacovoni

Paul Sabatier University - Toulouse III, Tolosa de Llenguadoc, Midi-Pyrénées, France

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Publications (32)200.25 Total impact

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    ABSTRACT: A high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet-unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORγt-deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORγt-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell metabolism 07/2015; 22(1):100-12. DOI:10.1016/j.cmet.2015.06.001 · 16.75 Impact Factor
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    ABSTRACT: Although both homologous recombination (HR) and nonhomologous end joining can repair DNA double-strand breaks (DSBs), the mechanisms by which one of these pathways is chosen over the other remain unclear. Here we show that transcriptionally active chromatin is preferentially repaired by HR. Using chromatin immunoprecipitation-sequencing (ChIP-seq) to analyze repair of multiple DSBs induced throughout the human genome, we identify an HR-prone subset of DSBs that recruit the HR protein RAD51, undergo resection and rely on RAD51 for efficient repair. These DSBs are located in actively transcribed genes and are targeted to HR repair via the transcription elongation-associated mark trimethylated histone H3 K36. Concordantly, depletion of SETD2, the main H3 K36 trimethyltransferase, severely impedes HR at such DSBs. Our study thereby demonstrates a primary role in DSB repair of the chromatin context in which a break occurs.
    Nature Structural & Molecular Biology 03/2014; 21(4). DOI:10.1038/nsmb.2796 · 11.63 Impact Factor
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    ABSTRACT: Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases.
    PLoS Genetics 09/2012; 8(9):e1002959. DOI:10.1371/journal.pgen.1002959 · 8.17 Impact Factor
  • Archives of Cardiovascular Diseases Supplements 01/2012; 4(1). DOI:10.1016/S1878-6480(12)70499-8
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    ABSTRACT: Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of gammaH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls gammaH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes gammaH2AX spreading. Remarkably, depletion of cohesin leads to an increase of gammaH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome.
    PLoS Genetics 01/2012; 8(1-1):e1002460. DOI:10.1371/journal.pgen.1002460 · 8.17 Impact Factor
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    ABSTRACT: Genomic DNA (gDNA) contamination is an inherent problem during RNA purification that can lead to non-specific amplification and aberrant results in reverse transcription quantitative PCR (RT-qPCR). Currently, there is no alternative to RT(-) controls to evaluate the impact of the gDNA background on RT-PCR data. We propose a novel method (ValidPrime) that is more accurate than traditional RT(-) controls to test qPCR assays with respect to their sensitivity toward gDNA. ValidPrime measures the gDNA contribution using an optimized gDNA-specific ValidPrime assay (VPA) and gDNA reference sample(s). The VPA, targeting a non-transcribed locus, is used to measure the gDNA contents in RT(+) samples and the gDNA reference is used to normalize for GOI-specific differences in gDNA sensitivity. We demonstrate that the RNA-derived component of the signal can be accurately estimated and deduced from the total signal. ValidPrime corrects with high precision for both exogenous (spiked) and endogenous gDNA, contributing ∼60% of the total signal, whereas substantially reducing the number of required qPCR control reactions. In conclusion, ValidPrime offers a cost-efficient alternative to RT(-) controls and accurately corrects for signals derived from gDNA in RT-qPCR.
    Nucleic Acids Research 01/2012; 40(7):e51. DOI:10.1093/nar/gkr1259 · 9.11 Impact Factor
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    ABSTRACT: Aims/hypothesisEvidence suggests that bacterial components in blood could play an early role in events leading to diabetes. To test this hypothesis, we studied the capacity of a broadly specific bacterial marker (16SrDNA) to predict the onset of diabetes and obesity in a general population. MethodsData from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) is a longitudinal study with the primary aim of describing the history of the metabolic syndrome. The 16S rDNA concentration was measured in blood at baseline and its relationship with incident diabetes and obesity over 9years of follow-up was assessed. In addition, in a nested case–control study in which participants later developed diabetes, bacterial phylotypes present in blood were identified by pyrosequencing of the overall 16S rDNA gene content. ResultsWe analysed 3,280 participants without diabetes or obesity at baseline. The 16S rDNA concentration was higher in those destined to have diabetes. No difference was observed regarding obesity. However, the 16S rDNA concentration was higher in those who had abdominal adiposity at the end of follow-up. The adjusted OR (95% CIs) for incident diabetes and for abdominal adiposity were 1.35 (1.11, 1.60), p = 0.002 and 1.18 (1.03, 1.34), p = 0.01, respectively. Moreover, pyrosequencing analyses showed that participants destined to have diabetes and the controls shared a core blood microbiota, mostly composed of the Proteobacteria phylum (85–90%). Conclusions/interpretation16S rDNA was shown to be an independent marker of the risk of diabetes. These findings are evidence for the concept that tissue bacteria are involved in the onset of diabetes in humans. KeywordsAbdominal adiposity–Microbiota–Obesity–16S rDNA gene
    Diabetologia 12/2011; 54(12):3055-3061. DOI:10.1007/s00125-011-2329-8 · 6.88 Impact Factor
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    ABSTRACT: The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.
    Gut 11/2011; 61(4):543-53. DOI:10.1136/gutjnl-2011-301012 · 13.32 Impact Factor
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    ABSTRACT: Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodeling. The goal was to explore the molecular basis of the response of skeletal muscle and adipose tissue during a short-term dexamethasone treatment to better understand the induction of side-effects of glucocorticoids on these metabolic tissues. Fifteen healthy male subjects were assigned to a 4-day treatment with dexamethasone at 4 mg/day. The primary outcome measures were changes in gene expression profiling of subcutaneous skeletal muscle and adipose tissue. Urinary cortisol, plasma, and metabolic biochemistry were also assessed. In both tissues the prominent observation was a response to stress and increased inflammatory responses. An upregulation of the serum amyloid A was detected in skeletal muscle, adipose tissue, and plasma, whereas circulating levels of C reactive protein, another acute phase protein, decreased along with a worsened insulin sensitivity index. As tissue-specific features, tissue remodeling was shown in skeletal muscle while the adipose tissue exhibited a decreased energy metabolism. Several limitations might be raised due to the small number of subjects investigated: a possible cross talk with the mineralocorticoid receptor, and a single time point may not identify regulations occurring during longitudinal treatment. In line with the known physiological effect of glucocorticoids the early modulation of stress response genes was observed. An unexpected feature was the upregulation of the inflammatory and immune pathways. The identification of novel impact on two glucocorticoid target tissues provides a molecular basis for the design of more specific glucocorticoids devoid of adverse effects.
    Physiological Genomics 11/2011; 44(2):141-51. DOI:10.1152/physiolgenomics.00032.2011 · 2.81 Impact Factor
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    ABSTRACT: The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers. 294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification. These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF.
    PLoS ONE 06/2011; 6(6):e20414. DOI:10.1371/journal.pone.0020414 · 3.53 Impact Factor
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    ABSTRACT: Objectif Des données expérimentales suggèrent que la présence de composants bactériens dans le sang et les tissus est une des étapes initiales conduisant au diabète de type 2. L’objectif de l’étude est d’analyser la relation entre la concentration sanguine d’un gène hautement conservé au sein des espèces bactériennes : le gène 16S ARNr et la survenue du diabète dans une population générale. Patients et méthodes L’étude DESIR est une étude de cohorte dont l’objectif était de décrire l’histoire naturelle du syndrome métabolique. Les participants ont été évalués à l’inclusion et à 3, 6 et 9 ans. La concentration sanguine du gène 16S ARNr a été mesurée à l’inclusion. De plus nous avons réalisé dans un sous groupe de la population une étude cas témoin pour identifier par technique de pyroséquençage, l’ADN bactérien associé à la survenue du diabète. Résultats 3 650 participants indemnes de diabète à l’inclusion ont été analysés. En référence au quartile de concentration sanguine d’ADN bactérien le plus faible et après ajustement sur les facteurs confondants, l’odds ratio de développer un diabète pour la dernière période de suivi était de 1,92 (0,76–4,81) dans le quartile 2, 3.50 (1,42–8,62) dans le quartile 3 and 3,63 (1,52–8,70) dans le quartile 4. L’analyse par pyroséquençage de l’ADN bactérien a montré que les sujets destinés à devenir diabétiques et les témoins partageaient le même ensemble de gènes bactériens appartenant pour l’essentiel au phylum des protéobactéries avec des différences au niveau des genres bactériens. Conclusion La concentration sanguine en gènes bactériens présents dans le sang est un marqueur de risque de développer un diabète. Le microbiome tissulaire pourrait être une cible thérapeutique pour prévenir les maladies métaboliques.
    Diabetes & Metabolism 03/2011; 37(1). DOI:10.1016/S1262-3636(11)70573-0 · 2.85 Impact Factor
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    Diabetes & Metabolism 03/2011; 37(1). DOI:10.1016/S1262-3636(11)70613-9 · 2.85 Impact Factor
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    ABSTRACT: DNA double strand breaks (DSBs) are among the most deleterious forms of lesions and deciphering the details of the chromatin landscape induced around DSBs represents a great challenge for molecular biologists. Chromatin Immunoprecipitation, followed by microarray hybridisation (ChIP-chip) or high-throughput sequencing (ChIP-seq), are powerful techniques that provide high-resolution maps of protein-genome interactions. However, applying these techniques to study chromatin changes induced around DSBs was previously hindered due to a lack of suitable DSB induction techniques. We have recently developed an experimental system utilizing a restriction enzyme fused to a modified oestrogen receptor ligand binding domain (AsiSI-ER), which generates multiple, sequence-specific and unambiguously positioned DSBs across the genome upon induction with 4-hydroxytamoxifen (4OHT).(1) Cell lines expressing this construct represent a powerful tool to study specific chromatin changes during DSB repair, enabling high-resolution profiling of DNA repair complexes and chromatin modifications induced around DSBs. Using this system, we have recently produced the first map of gammaH2AX, a DSB-induced chromatin modification, on two human chromosomes and have investigated its spreading properties.(1) Here we provide additional data characterizing the cell lines, present a genome-wide profile of gammaH2AX obtained by ChIP-seq, and discuss the potential of our system towards investigations of previously uncharacterized aspects of DSB repair.
    Cell cycle (Georgetown, Tex.) 08/2010; 9(15):2963-72. DOI:10.4161/cc.9.15.12412 · 5.01 Impact Factor
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    ABSTRACT: Chromatin acts as a key regulator of DNA-related processes such as DNA damage repair. Although ChIP-chip is a powerful technique to provide high-resolution maps of protein–genome interactions, its use to study DNA double strand break (DSB) repair has been hindered by the limitations of the available damage induction methods. We have developed a human cell line that permits induction of multiple DSBs randomly distributed and unambiguously positioned within the genome. Using this system, we have generated the first genome-wide mapping of γH2AX around DSBs. We found that all DSBs trigger large γH2AX domains, which spread out from the DSB in a bidirectional, discontinuous and not necessarily symmetrical manner. The distribution of γH2AX within domains is influenced by gene transcription, as parallel mappings of RNA Polymerase II and strand-specific expression showed that γH2AX does not propagate on active genes. In addition, we showed that transcription is accurately maintained within γH2AX domains, indicating that mechanisms may exist to protect gene transcription from γH2AX spreading and from the chromatin rearrangements induced by DSBs.
    The EMBO Journal 03/2010; 29(8):1446-1457. DOI:10.1038/emboj.2010.38 · 10.75 Impact Factor
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    ABSTRACT: Uncoupling protein (UCP) 3 is an inner mitochondrial membrane transporter mainly produced in skeletal muscle in humans. UCP3 plays a role in fatty acid metabolism and energy homeostasis and modulates insulin sensitivity. In humans, UCP3 content is higher in fast-twitch glycolytic muscle than in slow-twitch oxidative muscle and is dysregulated in type 2 diabetes. Here, we studied the molecular mechanisms determining human UCP3 levels in skeletal muscle and their regulation by fasting in transgenic mice. We produced a series of transgenic lines with constructs bearing different putative regulatory regions of the human UCP3 gene, including promoter and intron sequences. UCP3 mRNA and reporter gene expression and activity were measured in different skeletal muscles and tissues. The profile of expression and the response to fasting and thyroid hormone of human UCP3 mRNA in transgenic mice with 16 kb of the human UCP3 gene were similar to that of the endogenous human gene. Various parts of the UCP3 promoter did not confer expression in transgenic lines. Inclusion of intron 1 resulted in an expression profile in skeletal muscle that was identical to that of human UCP3 mRNA. Further dissection of intron 1 revealed that distinct regions were involved in skeletal muscle expression, distribution among fibre types and response to fasting. The control of human UCP3 transcription in skeletal muscle is not solely conferred by the promoter, but depends on several cis-acting elements in intron 1, suggesting a complex interplay between the promoter and intronic sequences.
    Diabetologia 06/2009; 52(8):1638-46. DOI:10.1007/s00125-009-1385-9 · 6.88 Impact Factor
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    ABSTRACT: Experiments with EMCV (Encephalomyocarditis virus) internal ribosome entry sites (IRESes) have shown that microRNAs (miRs) are unable to inhibit IRES driven translation. However, it is accepted that miRs can inhibit translation through multiple mechanisms, only some of which require interaction with the 5' cap structure. In this report, we first validate the targeting of miR-16 to a predicted binding site in the VEGF 3'UTR. We developed a series of experiments to ascertain whether or not miR-16 can inhibit translation of transcripts driven by either of the VEGF IRESes. Our results indicate that cellular IRESes can be classified as both sensitive and insensitive to miR control. While VEGF IRES-A activity was not altered by miR-16 targeting to the 3'UTR, IRES-B was susceptible to miR-16 inhibition. Taken together with previous results that show that IRES-B selectively translates the CUG initiated VEGF-121 isoform, we can conclude that the existence of two differentially susceptible IRESes in the VEGF 5'UTR leads to even more complex regulatory control of VEGF isoform production. This study demonstrates for the first time the inhibition of cellular IRES driven translation by a miR.
    RNA 03/2009; 15(2):249-54. DOI:10.1261/rna.1301109 · 4.62 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor-A (VEGF), a powerful factor involved in vasculogenesis and angiogenesis, is translationally regulated through 2 independent internal ribosome entry sites (IRESs A and B). IRESs enable an mRNA to be translated under conditions in which 5'-cap-dependent translation is inhibited, such as low oxygen stress. In the VEGF mRNA, IRES A influences translation at the canonical AUG codon, whereas the 5' IRES B element regulates initiation at an upstream, in frame CUG. In this study, we have developed transgenic mice expressing reporter genes under the control of these 2 IRESs. We reveal that although these IRESs display low activity in embryos and adult tissues, they permit efficient translation at early time points in ischemic muscle, a stress under which cap-dependent translation is inhibited. These results demonstrate the in vivo efficacy of the VEGF IRESs in response to a local environmental stress such as hypoxia.
    Circulation Research 03/2007; 100(3):305-8. DOI:10.1161/01.RES.0000258873.08041.c9 · 11.09 Impact Factor
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    ABSTRACT: Targets of the oncogenic transcription factor v-Jun in the murine cell line C3H 10T1/2 cells have been identified using DNA microarrays. Two targets, Akap12 and Marcks, are downregulated in transformed cells and are known tumor suppressor genes. Overexpression of either Akap12 or Marcks in v-Jun-transformed cells reverses the transformed phenotype and leads to the re-expression of the other tumor suppressor gene, suggesting that these two genes cooperate in the establishment of the nontransformed state. Reverted cells continue to express v-Jun at high levels and also re-express c-Jun, which is normally repressed by v-Jun. A panel of six cell lines has been generated to evaluate the expression levels of other v-Jun targets in 10T1/2 cells. With these cells, we find that the upregulated target Sprr1a has an expression pattern that correlates with the transformed phenotype.
    Oncogene 08/2004; 23(33):5703-6. DOI:10.1038/sj.onc.1207737 · 8.56 Impact Factor
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    ABSTRACT: BARX2 is a homeobox transcription factor that influences cellular differentiation in various developmental contexts. To begin to identify the gene targets that mediate its effects, chromatin immunoprecipitation (ChIP) was used to isolate BARX2 binding sites from the human MCF7 breast cancer cell line. Cloning and sequencing of BARX2-ChIP-derived DNA fragments identified 60 potential BARX2 target loci that were proximal to or within introns of genes involved in cytoskeletal organization, cell adhesion, growth factor signaling, transcriptional regulation, and RNA metabolism. The sequences of over half of the fragments showed homology with the mouse genome, and several sequences could be mapped to orthologous human and mouse genes. Binding of BARX2 to 21 genomic loci examined was confirmed quantitatively by replicate ChIP assays. A combination of sequence analysis and electrophoretic mobility shift assays revealed homeodomain binding sites within several fragments that bind to BARX2 in vitro. The majority of BARX2 binding fragments tested (14/19), also affected transcription in luciferase reporter gene assays. Mutation analyses of three fragments showed that their transcriptional activities required the HBS, and suggested that BARX2 regulates gene expression by binding to DNA elements containing paired TAAT motifs that are separated by a poly(T) sequence. Inhibition of BARX2 expression in MCF7 cells led to reduced expression of eight genes associated with BARX2 binding sites, indicating that BARX2 directly regulates their expression. The data suggest that BARX2 can coordinate the expression of a network of genes that influence the growth of MCF7 cells.
    Journal of Biological Chemistry 05/2004; 279(15):14520-30. DOI:10.1074/jbc.M310259200 · 4.60 Impact Factor
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    ABSTRACT: The vascular endothelial growth factor-A (VEGF) gene locus contains eight exons that span 14 kb. Alternative splicing generates multiple, different mRNAs that in turn translate into at least five protein isoforms. While the canonical AUG start codon is located at position 1039 in exon 1, there also exists an upstream, in-frame CUG initiation codon that drives expression of L-VEGF, containing an additional 180 amino acids. Two separate internal ribosome entry sites (IRES) regulate the activity of each initiation codon. Thus the 5'-UTR of VEGF, which comprises the majority of exon 1, consists of IRES B, the CUG, IRES A, and the AUG, from 5' to 3'. Previously, it has been shown that IRES B regulates initiation at the CUG and IRES A regulates AUG usage. In this study, we have found evidence that the exon content of the VEGF mRNA, determined through alternative splicing, controls IRES A activity. While the CUG is most efficient at initiating translation, transcripts that lack both exons 6 and 7 and therefore contain an exon 5/8 junction lack AUG-initiated translation. The process of splicing is not responsible for this start codon selection since transfection of genomic and cDNA VEGF sequences give the same expression pattern. We hypothesize that long range tertiary interactions in the VEGF mRNA regulate IRES activity and thus control start codon selection. This is the first report describing the influence of alternatively spliced coding sequences on codon selection by modulating IRES activity.
    Journal of Biological Chemistry 05/2004; 279(18):18717-26. DOI:10.1074/jbc.M308410200 · 4.60 Impact Factor

Publication Stats

932 Citations
200.25 Total Impact Points

Institutions

  • 2011–2012
    • Paul Sabatier University - Toulouse III
      • Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse - UMRS 1048 - I2MC
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2009–2012
    • University of Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2009–2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1997–2004
    • The Scripps Research Institute
      • • Department of Molecular and Experimental Medicine
      • • Department of Cell and Molecular Biology
      La Jolla, California, United States