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ln this work, we attempted to determine the function of SZRDl,a protein of unknown function using a multidimensional approach. Our selection of SZRDl was based on the presence of four putative binding sites for miR-128 in its 3'UTR.Mi-RNAs are small RNAs that inhibit translation and promote mRNA degradation of target transcripts. They usually have many targets, but effects on individual targets are often modest. Small changes in target transcripts are therefore thought to collaborate to lead to a cellular function. We therefore hypothesized that uncharacterized targets of a mi-RNA might functionally collaborate with other targets of the same mi-RNA. To test this hypothesis we focused on miR-128 and one of its predicted targets of unknown function, SZRDl. MiR-128 targets are implicated in cellular signaling pathways and in a RNA quality control mechanism called Nonsense-Mediated Decay (NMD). we hypothesized that SZRDl could be implicated in the function’s exerted by miR-128.First, we demonstrated that the conserved multiple binding site of miR-128 in the 3'UTR of SZRDl are indeed functional using luciferase reporter genes.The analysis of SZRDl protein function followed a multidimensional approach based on primary sequence analysis, existing high-throughput data and identification of possible partners through tandem affinity purification followed by mass spectrometry:The SZRDl gene gives rise to several transcripts that code for proteins of 133 and 154 amino acids (SZRDl Long and SZRDl Short). We showed that SZRDl Long is excluded from the nuclei, possibly through a predicted nuclear export sequence (NES), and that SZRDl Short is phosphorylated in a cell cycle-dependent manner.We identified several proteins implicated in various aspects of RNA metabolism as interactors of SZRDl: RENTl/UPFl,STRAP, ClQBP, UNR/CSDEl and GEMIN2.We provide preliminary evidence that SZRDl might regulate the function of its interactors RENTl/UPFl and STRAP.Notably, RENTl/UPFl has previously been identified as a target of miR-128. Our data therefore are consistent with the hypothesisthat target genes of miR-128 functionally collaborate. Dans le cadre de ce mémoire, nous avons cherché à établir la fonction de SZRDl en utilisant une approche multidimensionelle. C'est la présence de quatre sites de liaisons potentiels au miR-128 dans la région 3'non traduite (3'UTR) de SZRDl qui a guidé notre choix vers cette protéine.Les mi-ARNs sont de courts ARNs simple brin qui inhibent la traduction et/ou favorisent la dégradation de leurs transcrits cibles. Dans la plupart des cas, chaque mi-ARN possède un grand nombre de cibles mais l'effet sur chacune d'entre elles est souvent modeste. Ilest donc possible que l'association de ces faibles mais nombreux changements ait une importance fonctionnelle. Nous avons donc émis l'hypothèse qu'une cible non caractérisée d'un mi-ARN pourraient collaborer avec d'autres cibles de ce même mi-ARN. Nous avons testé cette hypothèse en étudiant le miR-128 et une de ses cibles prédites mais dont la fonction est inconnue, SZRDl. Les cibles connues du miR-128 jouent un rôle dans la signalisation cellulaire et dans un mécanisme de contrôle de la qualité des ARNs appelé « Nonsense-Mediated Decay » ou NMD. Dès lors, nous avons émis l'hypothèse selon laquelle la protéine SZRDl pourrait être impliquée dans les fonctions connues de miR-128.Nous avons tout d'abord démontré, grâce à un test rapporteur luciférase, que les sites de liaisons conservés pour le miR-128 présents dans la région 3'UTR de SZRDl sont fonctionnels et que SZRDl semble bien être une cible du miR-128. Afin de déterminer la fonction de SZRDl,nous avons utilisé une approche multidimensionnelle basée sur l'analyse de la séquence primaire en résidus aminés de la protéine, sur des données issues d'analyses à haut débit et sur l'identification de partenaires potentiels par purification d'affinité en tandem suivie de spectrométrie de masse :Le gène SZRDl donne lieu à plusieurs transcrits codants pour des protéines de 133 et 154 résidus aminés (SZRDl Courte et SZRDl Longue, respectivement) . Nous avons montré que SZRDl Longue peut être exclue du noyau, probablement dû à la présence d'une séquence d'export nucléaire (NES) et que SZRDl Courte est phosphorylée à certains stades du cycle cellulaire.Nous avons identifié plusieurs protéines interactantes de SZRDl qui sont impliquées à différents niveaux du métabolisme de I'ARN : RENTl/UPFl, STRAP, ClQBP, UNR/CSDl et GEMIN2.Nous avons obtenus des données préliminaires suggérant que SZRDl est capable de réguler,la fonction de certaines de ses protéines partenaires comme RENTl/UPFl et STRAP.Il est important de noter que RENTl/UPFl a également été décrit comme étant une cible du miR- 1Nos données sont donc en accord avec l'hypothèse selon laquelle les gènes cibles du miR- 128 collaborent fonctionnellement.

MIRN128 microRNA, human --- RNA Processing, Post-Transcriptional

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Long non-coding RNAs (lnc)RNAs have emerged as a new paradigm in epigenetic regulation of the genome. Thousands of lncRNAs have been identified and observed in a wide range of organisms. Unlike mRNA, lncRNA have no protein-coding capacity. So, while their function is not entirely clear, they may serve as key organizers of protein complexes that allow for higher order regulatory events. Discovering these functions has been the result of intense research done of the last few years, and lncRNA research has had several critical developments during that time. This book consolidates these ideas and models to better examine the most important issues in lncRNA biology. This includes critical studies that have led to the discovery and annotation of lncRNAs in numerous species, and the molecular mechanisms for a few lncRNA that have begun to emerge.

Molecular biology. --- Non-coding RNA. --- RNA, Untranslated. --- Non-coding RNA --- Molecular biology --- Biology --- Biological Science Disciplines --- Natural Science Disciplines --- Disciplines and Occupations --- Physiology --- Genetics --- Medicine --- Health & Biological Sciences --- Pathology --- Molecular aspects. --- fRNA --- Functional RNA --- ncRNA --- nmRNA --- Non-messenger RNA --- Non-translated RNA --- Noncoding RNA --- Nontranslated RNA --- Small non-messenger RNA --- Small RNA --- snmRNA --- sRNA --- Untranslated RNA --- Molecular biochemistry --- Molecular biophysics --- Medicine. --- Human genetics. --- Proteins. --- Biomedicine. --- Human Genetics. --- Biomedicine general. --- Protein Science. --- RNA --- Biochemistry --- Biophysics --- Biomolecules --- Systems biology --- Biochemistry. --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Chemistry --- Medical sciences --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Physicians --- Heredity, Human --- Physical anthropology --- Composition --- Health Workforce --- Proteins . --- Biomedicine, general. --- Proteids --- Polypeptides --- Proteomics

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RNA, Messenger. --- Translational Medical Research. --- Messenger RNA --- Genetic translation --- Translation (Genetics) --- Informational RNA --- Messenger ribonucleic acid --- mRNA --- Protein transcript --- Protein transcripts --- Template RNA --- Knowledge Translation --- Translational Medical Science --- Translational Medicine --- Translational Research, Medical --- Translational Research --- Knowledge Translations --- Medical Research, Translational --- Medical Science, Translational --- Medical Sciences, Translational --- Medical Translational Research --- Medicine, Translational --- Research, Medical Translational --- Research, Translational --- Research, Translational Medical --- Science, Translational Medical --- Sciences, Translational Medical --- Translation, Knowledge --- Translational Medical Sciences --- Translational Researchs --- Translations, Knowledge --- Non-Polyadenylated mRNA --- Poly(A) RNA --- Polyadenylated mRNA --- Messenger RNA, Polyadenylated --- Poly(A) Tail --- Poly(A)+ RNA --- Poly(A)+ mRNA --- RNA, Messenger, Polyadenylated --- RNA, Polyadenylated --- mRNA, Non-Polyadenylated --- mRNA, Polyadenylated --- Non Polyadenylated mRNA --- Polyadenylated Messenger RNA --- Polyadenylated RNA --- RNA, Polyadenylated Messenger --- mRNA, Non Polyadenylated --- Genetic translation. --- Genetic code --- Genetic regulation --- RNA --- National Center for Advancing Translational Sciences (U.S.) --- Translational Research, Biomedical --- Translational Research, Biomedical.

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This book reflects the current state of knowledge about the role of microRNAs in the formation and progression of solid tumours. The main focus lies on computational methods and their applications in combination with cutting edge experimental techniques that are used to approach all aspects of microRNA regulation in cancer. The use of high-throughput quantitative techniques makes an integrative experimental and computational approach necessary. This book will be a resource for researchers starting out with microRNA research, but is also intended for the experienced researcher who wants to incorporate concepts and tools from systems biology and bioinformatics into his work. Bioinformaticians and modellers are provided with a general perspective on microRNA biology, and the state-of-the-art in computational microRNA biology.

Cancer -- Genetic aspects. --- Cancer. --- MicroRNA. --- Small interfering RNA --- Cancer --- Genomics --- Bioinformatics --- Biology --- Diseases --- Biochemical Processes --- RNA, Antisense --- Genetic Techniques --- Gene Expression Regulation --- Investigative Techniques --- Biological Science Disciplines --- Genetic Processes --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Biochemical Phenomena --- Antisense Elements (Genetics) --- Natural Science Disciplines --- Chemical Phenomena --- Nucleic Acids, Nucleotides, and Nucleosides --- Genetic Phenomena --- Phenomena and Processes --- Disciplines and Occupations --- Chemicals and Drugs --- Signal Transduction --- MicroRNAs --- Neoplasms --- Methods --- Gene Expression Profiling --- Computational Biology --- Gene Expression Regulation, Neoplastic --- Genetics --- Medicine --- Health & Biological Sciences --- Oncology --- Research --- Genetic aspects --- Data processing --- Bioinformatics. --- Research. --- Data processing. --- Bio-informatics --- Biological informatics --- Genome research --- Genomes --- Cancers --- Carcinoma --- Malignancy (Cancer) --- Malignant tumors --- piRNA (Piwi-interacting RNA) --- Piwi-interacting RNA --- Piwi protein-interacting RNA --- rasiRNA (Repeat-associated small interfering RNA) --- Repeat-associated siRNA --- Repeat-associated small interfering RNA --- Scan RNA --- scnRNA (Small scan RNA) --- Short hairpin RNA --- Short interfering RNA --- shRNA (Short hairpin RNA) --- siRNA (Small interfering RNA) --- Small hairpin RNA --- Small scan RNA --- tasiRNA (Trans-acting small interfering RNA) --- Trans-acting siRNA --- Trans-acting small interfering RNA --- Medicine. --- Cancer research. --- Gene expression. --- Molecular biology. --- Systems biology. --- Biomedicine. --- Cancer Research. --- Computational Biology/Bioinformatics. --- Systems Biology. --- Molecular Medicine. --- Gene Expression. --- Information science --- Computational biology --- Systems biology --- Biological systems --- Molecular biology --- Molecular biochemistry --- Molecular biophysics --- Biochemistry --- Biophysics --- Biomolecules --- Genes --- Genetic regulation --- Cancer research --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Expression --- Molecular genetics --- Tumors --- Antisense RNA --- Oncology. --- Biological models. --- Models, Biological

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Dna --- Genes. --- Genes. --- Genetic processes. --- Genetics. --- Genome. --- Proteins --- Rna --- Genetics. --- Genetics. --- Genetics.