Translational and structural requirements of the early nodulin gene enod40, a short-open reading frame-containing RNA, for elicitation of a cell-specific growth response in the alfalfa root cortex

A diversity of mRNAs containing only short open reading frames (sORF-RNAs; encoding less than 30 amino acids) have been shown to be induced in growth and differentiation processes. The early nodulin gene enod40, coding for a 0.7-kb sORF-RNA, is expressed in the nodule primordium developing in the root cortex of leguminous plants after infection by symbiotic bacteria. Ballistic microtargeting of this gene into Medicago roots induced division of cortical cells. Translation of two sORFs (I and II, 13 and 27 amino acids, respectively) present in the conserved 5* and 3* regions of enod40 was required for this biological activity. These sORFs may be translated in roots via a reinitiation mechanism. In vitro translation products starting from the ATG of sORF I were detectable by mutating enod40 to yield peptides larger than 38 amino acids. Deletion of a Medicago truncatula enod40 region between the sORFs, spanning a predicted RNA structure, did not affect their translation but resulted in significantly decreased biological activity. Our data reveal a complex regulation of enod40 action, pointing to a role of sORF-encoded peptides and structured RNA signals in developmental processes involving sORF-RNA

Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure

Background: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients. Methodology/Principal Findings: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations. Conclusions/Significance: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function

Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure

BACKGROUND: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10-15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.¦METHODOLOGY/PRINCIPAL FINDINGS: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LOD(max) of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.¦CONCLUSIONS/SIGNIFICANCE: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function

Caractérisation fonctionnelle des gènes Terminal Ear like au sein de la lignée verte

La conquête terrestre par les Plantes s est accompagnée d une augmentation importante de leur taille et d une répartition des fonctions au sein de tissus ou d organes spécialisés. Cette complexification cellulaire, associée à l allongement de la phase sporophytique au détriment de la phase gamétophytique, a nécessité le recrutement et l évolution de nombreux gènes. Afin de mieux comprendre la mise en place de ces mécanismes, nous avons orienté nos travaux vers les gènes TEL codant pour des protéines de liaison aux ARN de type RRM. En effet, ils constituent de bons candidats, n étant présents que chez les Végétaux Terrestres et régulant la mise en place des organes floraux et foliaires chez les Poacées. Ainsi, nous avons initié la caractérisation fonctionnelle des gènes TEL au sein de la Lignée Verte. L étude de transformants exprimant des versions tronquées de l unique gène PpTEL nous a permis de montrer que chez la mousse Physcomitrella patens, ce gène contrôlait négativement la croissance des protonémas et des sporophytes, alors qu il régule positivement l initiation et le développement des pieds feuillés. Chez Arabidopsis thaliana, la caractérisation de nombreux mutants a permis de mettre en évidence un rôle-clé pour AtTEL1 et AtTEL2 dans la régulation positive de la croissance végétative et l induction florale, alors que ces gènes contrôlent négativement la formation des fleurs. En outre, nous avons pu montré que les gènes TEL seraient potentiellement des senseurs métaboliques, capables de réguler la division cellulaire et donc la croissance de la plante, en fonction de l énergie disponible pour celle-ci.The land colonisation by plants was accompanied by an enormous increase in their size and the sharing out of functions within specialised tissues and organs. This cellular complexification, associated with the rise to dominance of the diploid phase (sporophyte) of the life cycle, required the recruitment and the evolution of many genes. In order to better understand the involved mechanisms, we focused our attention on TEL genes which encode RRM-type RNA-binding proteins. Indeed, they appeared as good candidates, since they are only present in land plants and they were shown to regulate the initiation of foliar and floral organs in Poaceae. So, the functional characterisation of TEL genes within the Green Lineage was initiated. The analysis of Physcomitrella patens mutants expressing truncated versions of the unique PpTEL gene allowed us to show that this gene was negatively controlling the growth of the protonema and the sporophytes, whereas it regulates positively the initiation and the development of gametophores. In Arabidopsis thaliana, the characterisation of TEL mutants highlighted a key role for AtTEL1 and AtTEL2 in the positive regulation of vegetative growth and floral transition, whereas they negatively control the development of flowers. Moreover, we could show that TEL genes would act as metabolic sensors, able to regulate cellular division and therefore the plant growth, depending on the available energy for the plant.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Impact of pre- and post-variant filtration strategies on imputation

International audienceQuality control (QC) methods for genome-wide association studies and fine mapping are commonly used for imputation, however they result in loss of many single nucleotide polymorphisms (SNPs). To investigate the consequences of filtration on imputation, we studied the direct effects on the number of markers, their allele frequencies, imputation quality scores and post-filtration events. We pre-phrased 1031 genotyped individuals from diverse ethnicities and compared the imputed variants to 1089 NCBI recorded individuals for additional validation. Without QC-based variant pre-filtration, we observed no impairment in the imputation of SNPs that failed QC whereas with pre-filtration there was an overall loss of information. Significant differences between frequencies with and without pre-filtration were found only in the range of very rare (5E−04–1E−03) and rare variants (1E−03–5E−03) (p < 1E−04). Increasing the post-filtration imputation quality score from 0.3 to 0.8 reduced the number of single nucleotide variants (SNVs) < 0.001 2.5 fold with or without QC pre-filtration and halved the number of very rare variants (5E−04). Thus, to maintain confidence and enough SNVs, we propose here a two-step filtering procedure which allows less stringent filtering prior to imputation and post-imputation in order to increase the number of very rare and rare variants compared to conservative filtration methods

Diversity and Evolution of CYCLOIDEA-Like TCP Genes in Relation to Flower Development in Papaveraceae

Monosymmetry evolved several times independently during flower evolution. In snapdragon (Antirrhinum majus), a key gene for monosymmetry is CYCLOIDEA (CYC), which belongs to the class II TCP gene family encoding transcriptional activators. We address the questions of the evolutionary history of this gene family and of possible recruitment of genes homologous to CYC in floral development and symmetry in the Papaveraceae. Two to three members of the class II TCP family were found in each species analyzed, two of which were CYC-like genes, on the basis of the presence of both the TCP and R conserved domains. The duplication that gave rise to these two paralogous lineages (named PAPACYL1 and PAPACYL2) probably predates the divergence of the two main clades within the Papaveraceae. Phylogenetic relationships among angiosperm class II TCP genes indicated that (1) PAPACYL genes were closest to Arabidopsis (Arabidopsis thaliana) AtTCP18, and a duplication at the base of the core eudicot would have given rise to two supplementary CYC-like lineages; and (2) at least three class II TCP genes were present in the ancestor of monocots and eudicots. Semiquantitative reverse transcription-polymerase chain reaction and in situ hybridization approaches in three species with different floral symmetry indicated that both PAPACYL paralogs were expressed during floral development. A pattern common to all three species was observed at organ junctions in inflorescences and flowers. Expression in the outer petals was specifically observed in the two species with nonactinomorphic flowers. Hypotheses concerning the ancestral pattern of expression and function of CYC-like genes and their possible role in floral development of Papaveraceae species leading to bisymmetric buds are discussed

Nuclear speckle RNA binding proteins remodel alternative splicing and the non-coding Arabidopsis transcriptome to regulate a cross-talk between auxin and immune responses

Nuclear speckle RNA binding proteins (NSRs) act as regulators of alternative splicing (AS) and auxin-regulated developmental processes such as lateral root formation in Arabidopsis thaliana. These proteins were shown to interact with specific alternatively spliced mRNA targets and at least with one structured lncRNA, named Alternative Splicing Competitor RNA. Here, we used genome-wide analysis of RNAseq to monitor the NSR global role on multiple tiers of gene expression, including RNA processing and AS. NSRs affect AS of 100s of genes as well as the abundance of lncRNAs particularly in response to auxin. Among them, the FPA floral regulator displayed alternative polyadenylation and differential expression of antisense COOLAIR lncRNAs in nsra/b mutants. This may explains the early flowering phenotype observed in nsra and nsra/b mutants. GO enrichment analysis of affected lines revealed a novel link of NSRs with the immune response pathway. A RIP-seq approach on an NSRa fusion protein in mutant background identified that lncRNAs are privileged direct targets of NSRs in addition to specific AS mRNAs. The interplay of lncRNAs and AS mRNAs in NSR-containing complexes may control the crosstalk between auxin and the immune response pathway

Etude LYMPHOREC. Réponse immunitaire intra-tumorale à la radiothérapie préopératoire pour des cancers du rectum de stades II-III: nouveau paramètre pronostic de la survie des patients

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Comparison of early and late MRI in neonatal hypoxic–ischemic encephalopathy using three assessment methods

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