Impaired Embryonic Development in Mice Overexpressing the RNA-Binding Protein TIAR

TIA-1-related (TIAR) protein is a shuttling RNA-binding protein involved in several steps of RNA metabolism. While in the nucleus TIAR participates to alternative splicing events, in the cytoplasm TIAR acts as a translational repressor on specific transcripts such as those containing AU-Rich Elements (AREs). Due to its ability to assemble abortive pre-initiation complexes coalescing into cytoplasmic granules called stress granules, TIAR is also involved in the general translational arrest observed in cells exposed to environmental stress. However, the in vivo role of this protein has not been studied so far mainly due to severe embryonic lethality upon tiar invalidation.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Temporally Regulated Traffic of HuR and Its Associated ARE-Containing mRNAs from the Chromatoid Body to Polysomes during Mouse Spermatogenesis

International audienceBACKGROUND: In mammals, a temporal disconnection between mRNA transcription and protein synthesis occurs during late steps of germ cell differentiation, in contrast to most somatic tissues where transcription and translation are closely linked. Indeed, during late stages of spermatogenesis, protein synthesis relies on the appropriate storage of translationally inactive mRNAs in transcriptionally silent spermatids. The factors and cellular compartments regulating mRNA storage and the timing of their translation are still poorly understood. The chromatoid body (CB), that shares components with the P. bodies found in somatic cells, has recently been proposed to be a site of mRNA processing. Here, we describe a new component of the CB, the RNA binding protein HuR, known in somatic cells to control the stability/translation of AU-rich containing mRNAs (ARE-mRNAs). METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of cell imagery and sucrose gradient fractionation, we show that HuR localization is highly dynamic during spermatid differentiation. First, in early round spermatids, HuR colocalizes with the Mouse Vasa Homolog, MVH, a marker of the CB. As spermatids differentiate, HuR exits the CB and concomitantly associates with polysomes. Using computational analyses, we identified two testis ARE-containing mRNAs, Brd2 and GCNF that are bound by HuR and MVH. We show that these target ARE-mRNAs follow HuR trafficking, accumulating successively in the CB, where they are translationally silent, and in polysomes during spermatid differentiation. CONCLUSIONS/SIGNIFICANCE: Our results reveal a temporal regulation of HuR trafficking together with its target mRNAs from the CB to polysomes as spermatids differentiate. They strongly suggest that through the transport of ARE-mRNAs from the CB to polysomes, HuR controls the appropriate timing of ARE-mRNA translation. HuR might represent a major post-transcriptional regulator, by promoting mRNA storage and then translation, during male germ cell differentiation

Breast Cancer Epigenetics: From DNA Methylation to microRNAs

Both appropriate DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity. In cancerous cells these “epigenetic belts” become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNA (cytosine-5)-methyltransferase 1 (Dnmt1), Dnmt3a and Dnmt3b are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. However, several lines of evidence indicate that further layers of gene regulation are critical coordinators of DNMT expression, catalytic activity and target specificity. Splice variants of DNMT transcripts have been detected which seem to modulate methyltransferase activity. Also, the DNMT mRNA 3′UTR as well as the coding sequence harbors multiple binding sites for trans-acting factors guiding post-transcriptional regulation and transcript stabilization. Moreover, microRNAs targeting DNMT transcripts have recently been discovered in normal cells, yet expression of these microRNAs was found to be diminished in breast cancer tissues. In this review we summarize the current knowledge on mechanisms which potentially lead to the establishment of a DNA hypermethylome in cancer cells

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

Procedure to optimize modified atmosphere packaging for fruit

La respiration de tissus végétaux vivants et la diffusion des gaz au travers du film d'emballage modifient la composition de l'atmosphère du produit frais conditionné. Cette atmosphère modifiée (AM) peut être bénéfique au stockage des tissus de fruit, mais si la perméance du film n'est pas correctement optimisée, l'AM peut être inefficace ou même nuisible. Pour définir les meilleures perméances du film d'emballage (ou perméabilités) pour O2, CO2 et la vapeur d'eau, le taux respiratoire du tissu végétal doit être mesuré en fonction de la température et de l'atmosphère, et les meilleures concentrations en O2 et CO2, pour assurer la durée de conservation optimale, doivent être déterminées. La meilleure combinaison des films, du type et des conditions d'emballage du produit frais et de la température de stockage peut être modélisée et vérifiée expérimentalement. Le document présente les méthodes de mesure du taux respiratoire du tissu végétal, puis l'influence de la température et l'influence en O2 et CO2 sur le contenu sont étudiées. Cela permet de déterminer les concentrations optimales en O2 et CO2 et les taux optimaux de transmission de gaz au travers du film d'emballage. Enfin, des expérimentations concernant la simulation des atmosphères modifiées sont décrites. La méthodologie présentée dans ce travail fournit des informations utiles pour répondre au besoin d'un meilleur emballage pour les fruits et légumes. (Résumé d'auteur

Respiratory parameters and sugar catabolism of mushroom (Agaricus bisporus Lange)

The respiration rate (RR) of mushroom (Agaricus bisporus Lange, strain X25) under air follows Arrhenius' law with an apparent activation energy of 43 400 J mol(-1) corresponding to a Q(10) of 2.9 between 10 and 20 degrees C. Oxygen from 20 to 1 kPa did not affect RR at temperatures ranging from 5 to 20 degrees C, confirming previous studies. The initial RR of mushroom (same cultivar, flush, growing conditions) measured 24 h after harvesting can vary from 1 to 2 mmol O-2 kg(-1) h(-1) at 10 degrees C. The apparent K-m value was below 0.1 kPa at 10 degrees C, and could not be estimated more accurately due to instrumental limitations. Decrease in dry matter of modified atmosphere-packed mushrooms matched the theoretical carbon consumption calculated from the constant respiration rate. Glucose and glycogen were rapidly catabolized, whereas mannitol consumption began 3 and 8 days after harvest at 20 and 10 degrees C, respectively. It was concluded that no extension of mushroom shelf life was attainable through modified atmosphere packaging. Controlling RH within the package is likely to be more effective