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The Superconducting Analyzer for MUlti-particles from RAdioIsotope (SAMURAI) Pion-Reconstruction and Ion-Tracker Time Projection Chamber (SπRIT TPC) was designed to enable measurements of heavy ion collisions with the SAMURAI spectrometer at the RIKEN radioactive isotope beam factory and provides constraints on the equation of state of neutron-rich nuclear matter. The SπRIT TPC has a 50.5 cm drift length and an 86.4 × 134.4 cm2 pad plane with 12 096 pads that are equipped with the generic electronics for TPCs. The SπRIT TPC allows for an excellent reconstruction of particles and provides isotopic resolution for pions and other light charged particles across a wide range of energy losses and momenta. The details of the SπRIT TPC are presented, along with discussion of the TPC performance based on cosmic rays and charged particles emitted in heavy ion collisions.
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Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42
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Undiagnosed rare diseases (URDs) account for a significant portion of the overall rare disease burden, depending upon the country. Hence, URDs represent an unmet medical need. A specific challenge posed by the ensemble of the URD patient cohort is the heterogeneity of its composition; the group, indeed, includes very rare, still unidentified conditions as well as clinical variants of recognized rare diseases. Exact disease recognition requires new approaches that cut across national and institutional boundaries, may need the implementation of methods new to diagnostics, and embrace clinical care and research. To address these issues, the Undiagnosed Diseases Network International (UDNI) was established in 2014, with the major aims of providing diagnoses to patients, implementing additional diagnostic tools, and fostering research on novel diseases, their mechanisms, and their pathways. The UDNI involves centres with internationally recognized expertise, and its scientific resources and know-how aim to fill the knowledge gaps that impede diagnosis, in particularly for ultra-rare diseases. Consequently, the UDNI fosters the translation of research into medical practice, aided by active patient involvement. The goals of the UDNI are to work collaboratively and at an international scale to: 1) provide diagnoses for individuals who have conditions that have eluded diagnosis by clinical experts; 2) gain insights into the etiology and pathogenesis of novel diseases; 3) contribute to standards of diagnosing unsolved patients; and 4) share the results of UDNI research in a timely manner and as broadly as possible.
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Salud Global , Servicios de Información/organización & administración , Cooperación Internacional , Enfermedades Raras/diagnóstico , Enfermedades no Diagnosticadas , Investigación Biomédica , Humanos , Enfermedades Raras/etiología , Factores de TiempoRESUMEN
We used Drosophila melanogaster macrophage-like Schneider 2 (S2) cells as a model to study cell-mediated innate immunity against infection by the opportunistic fungal pathogen Candida albicans. Transcriptional profiling of S2 cells coincubated with C. albicans cells revealed up-regulation of several genes. One of the most highly up-regulated genes during this interaction is the D. melanogaster translational regulator 4E-BP encoded by the Thor gene. Analysis of Drosophila 4E-BP(null) mutant survival upon infection with C. albicans showed that 4E-BP plays an important role in host defense, suggesting a role for translational control in the D. melanogaster response to C. albicans infection.
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Candida albicans/fisiología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/microbiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Factores de Iniciación de Péptidos/metabolismo , Animales , Candidiasis , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Determinación de Punto Final , Regulación de la Expresión Génica , Genes de Insecto , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación/genética , Factores de Iniciación de Péptidos/genética , Fagocitosis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Supervivencia , Transcripción GenéticaRESUMEN
Translational control is a key genetic regulatory mechanism underlying the initial establishment of the major spatial axes of the Drosophila embryo. Many translational control mechanisms target eIF4E (eukaryotic initiation factor 4E), an initiation factor that recognizes the 5'-cap structure of the mRNA. Cap recognition by eIF4E, in complex with eIF4G, is essential for recruitment of the mRNA to the small ribosomal subunit. One established mechanism for repressing translation involves eIF4E-binding proteins, which competitively inhibit the eIF4E-eIF4G interaction. Our group has uncovered a novel mechanism for repression in which an eIF4E cognate protein called d4EHP, which cannot bind eIF4G, binds to the 5'-cap structure of cad mRNA thus rendering it translationally inactive. These two related, but distinct, mechanisms are discussed and contrasted in this review.
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Drosophila melanogaster/genética , Regulación de la Expresión Génica , Biosíntesis de Proteínas , Caperuzas de ARN/metabolismo , ARN Mensajero/metabolismo , Animales , Proteínas de Drosophila/metabolismo , Factor 4E Eucariótico de Iniciación/metabolismo , Factor 4G Eucariótico de Iniciación/metabolismo , Unión Proteica , Proteínas de Unión al ARN/metabolismoRESUMEN
Approximately three-quarters of human disease loci have counterparts in the fruit fly Drosophila melanogaster. This model organism is therefore extremely valuable for using to understand the role of these loci in normal development, and for unravelling genetic pathways in which these loci take part. Important advantages for Drosophila in such studies are its completed genome, the unparalleled collection of mutations already in existence, the relative ease in which new mutations can be generated, the existence of convenient techniques for inactivating or overexpressing genes in dispensable tissues that are easily observed and measured, and the ability to readily carry out second-site modifier genetics. Recent work in Drosophila on the insulin-signaling pathway, a pathway of profound clinical importance, is reviewed as an illustration of how such research can provide fundamental insights into the functions of this pathway in regulating growth and development. Moreover, Drosophila research is now identifying heretofore unknown regulators of insulin signaling, as well as indicating novel functions for this pathway in suppressing benign tumor formation and regulating life span.
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Diabetes Mellitus/genética , Drosophila melanogaster/genética , Animales , Perfilación de la Expresión Génica , Modelos AnimalesRESUMEN
Translational control is a prevalent means of gene regulation during Drosophila oogenesis and embryogenesis. Multiple maternal mRNAs are localized within the oocyte, and this localization is often coupled to their translational regulation. Subsequently, translational control allows maternally deposited mRNAs to direct the early stages of embryonic development. In this review we outline some general mechanisms of translational regulation and mRNA localization that have been uncovered in various model systems. Then we focus on the posttranscriptional regulation of four maternal transcripts in Drosophila that are localized during oogenesis and are critical for embryonic patterning: bicoid (bcd), nanos (nos), oskar (osk), and gurken (grk). Cis- and trans-acting factors required for the localization and translational control of these mRNAs are discussed along with potential mechanisms for their regulation.
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Drosophila/genética , Embrión no Mamífero/fisiología , Oocitos/fisiología , Biosíntesis de Proteínas/genética , ARN Mensajero/metabolismo , Animales , Transporte Biológico , Drosophila/embriología , Drosophila/metabolismo , Femenino , Predicción , Regulación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , ARN Mensajero/genéticaRESUMEN
With the completion of the Drosophila genome sequence, an important next step is to extract its biological information by systematic functional analysis of genes. We have produced a high-resolution genetic map of cytological region 38 of Drosophila using 41 deficiency stocks that provide a total of 54 breakpoints within the region. Of a total of 45 independent P-element lines that mapped by in situ hybridization to the region, 14 targeted 7 complementation groups within the 38 region. Additional EMS, X-ray, and spontaneous mutations define a total of 17 complementation groups. Because these two pools partially overlap, the completed analysis revealed 21 distinct complementation groups defined by point mutations. Seven additional functions were defined by trans-heterozygous combinations of deficiencies, resulting in a total of 28 distinct functions. We further produced a developmental expression profile for the 760 kb from 38B to 38E. Of 135 transcription units predicted by GENSCAN, 22 have at least partial homology to mobile genetic elements such as transposons and retroviruses and 17 correspond to previously characterized genes. We analyzed the developmental expression pattern of the remaining genes using poly(A)(+) RNA from ovaries, early and late embryos, larvae, males, and females. We discuss the correlation between GENSCAN predictions and experimentally confirmed transcription units, the high number of male-specific transcripts, and the alignment of the genetic and physical maps in cytological region 38.
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Mapeo Cromosómico , Drosophila/genética , Genoma , Animales , Secuencia de Bases , Northern Blotting , Southern Blotting , Bases de Datos como Asunto , Etiquetas de Secuencia Expresada , Prueba de Complementación Genética , Heterocigoto , Modelos Genéticos , Datos de Secuencia Molecular , Mutación , Mapeo Físico de Cromosoma , Mutación Puntual , Poli A , Programas InformáticosRESUMEN
The initiation factor 4E for eukaryotic translation (eIF4E) binds the messenger RNA 5'-cap structure and is important in the regulation of protein synthesis. Mammalian eIF4E activity is inhibited when the initiation factor binds to the translational repressors, the 4E-binding proteins (4E-BPS). Here we show that the Drosophila melanogaster 4E-BP (d4E-BP) is a downstream target of the phosphatidylinositol-3-OH kinase (PI(3)K) signal-transduction cascade, which affects the interaction of d4E-BP with eIF4E. Ectopic expression of a highly active d4E-BP mutant in wing-imaginal discs causes a reduction of wing size, brought about by a decrease in cell size and number. A marked reduction in cell size was also observed in post-mitotic cells. Expression of d4E-BP in the eye and wing together with PI(3)K or dAkt1, the serine/threonine kinase downstream of PI(3)K, resulted in suppression of the growth phenotype elicited by these kinases. Our results support a role for d4E-BP as an effector of cell growth.
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Proteínas Portadoras/fisiología , Drosophila melanogaster/metabolismo , Fosfatidilinositol 3-Quinasas/fisiología , Fosfoproteínas/fisiología , Transducción de Señal/fisiología , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/química , Proteínas Portadoras/genética , División Celular/fisiología , Clonación Molecular , Proteínas de Drosophila , Drosophila melanogaster/citología , Drosophila melanogaster/enzimología , Péptidos y Proteínas de Señalización Intracelular , Datos de Secuencia Molecular , Factores de Iniciación de Péptidos , Fosfoproteínas/química , Fosfoproteínas/genética , Biosíntesis de Proteínas , Homología de Secuencia de AminoácidoRESUMEN
Long-term synaptic plasticity may be associated with structural rearrangements within the neuronal circuitry. Although the molecular mechanisms governing such activity-controlled morphological alterations are mostly elusive, polysomal accumulations at the base of developing dendritic spines and the activity-induced synthesis of synaptic components suggest that localized translation is involved during synaptic plasticity. Here we show that large aggregates of translational components as well as messenger RNA of the postsynaptic glutamate receptor subunit DGluR-IIA are localized within subsynaptic compartments of larval neuromuscular junctions of Drosophila melanogaster. Genetic models of junctional plasticity and genetic manipulations using the translation initiation factors eIF4E and poly(A)-binding protein showed an increased occurrence of subsynaptic translation aggregates. This was associated with a significant increase in the postsynaptic DGluR-IIA protein levels and a reduction in the junctional expression of the cell-adhesion molecule Fasciclin II. In addition, the efficacy of junctional neurotransmission and the size of larval neuromuscular junctions were significantly increased. Our results therefore provide evidence for a postsynaptic translational control of long-term junctional plasticity.
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Regulación de la Expresión Génica , Unión Neuromuscular/fisiología , Biosíntesis de Proteínas , Sinapsis/fisiología , Animales , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Factor 4E Eucariótico de Iniciación , Larva , Potenciación a Largo Plazo/genética , Potenciación a Largo Plazo/fisiología , Mutación , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Unión Neuromuscular/embriología , Factores de Iniciación de Péptidos/biosíntesis , Factores de Iniciación de Péptidos/fisiología , Proteínas de Unión a Poli(A) , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/biosíntesis , Receptores AMPA/genética , Receptores AMPA/metabolismoRESUMEN
The Drosophila gene vasa (vas) encodes an RNA-binding protein required for embryonic patterning and germ cell specification. In vas mutants, translation of several germline mRNAs is reduced. Here we show that VAS interacts directly with the Drosophila homolog of yeast translation initiation factor 2, encoded by a novel gene, dIF2. Embryos produced by vas/+; dIF2/+ females have pattern defects and fewer germline progenitor cells, indicating a functional interaction between endogenous vas and dIF2 activities. Mutations in other translation initiation factors do not enhance the vas phenotype, suggesting that dIF2 has a particular role in germ plasm function. We conclude that VAS regulates translation of germline mRNAs by specific interaction with dIF2, an essential factor conserved from bacteria to humans.
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Drosophila melanogaster/genética , Factor 2 Eucariótico de Iniciación/genética , ARN Helicasas/genética , ARN Helicasas/metabolismo , Secuencia de Aminoácidos , Animales , ARN Helicasas DEAD-box , Proteínas de Drosophila , Drosophila melanogaster/embriología , Drosophila melanogaster/enzimología , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 4A Eucariótico de Iniciación , Factor 4E Eucariótico de Iniciación , Exones , Femenino , Heterocigoto , Datos de Secuencia Molecular , Mutación , Factores de Iniciación de Péptidos/genética , ARN Helicasas/química , Proteínas Recombinantes/metabolismo , Mapeo Restrictivo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Alineación de SecuenciaRESUMEN
In all animals information is passed from parent to offspring via the germline, which segregates from the soma early in development and undergoes a complex developmental program to give rise to the adult gametes. Many aspects of germline development have been conserved throughout the animal kingdom. Here we review the unique properties of germ cells, the initial determination of germ cell fates, the maintenance of germ cell identity, the migration of germ cells to the somatic gonadal primordia and the proliferation of germ cells during development invertebrates and invertebrates. Similarities in germline development in such diverse organisms as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis and Mus musculus will be highlighted.
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Proteínas de Drosophila , Regulación del Desarrollo de la Expresión Génica/fisiología , Células Germinativas/fisiología , Invertebrados/embriología , Vertebrados/embriología , Animales , Caenorhabditis elegans/embriología , Caenorhabditis elegans/genética , Caenorhabditis elegans/crecimiento & desarrollo , Linaje de la Célula , Movimiento Celular , Polaridad Celular , ARN Helicasas DEAD-box , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Embrión no Mamífero/fisiología , Femenino , Gónadas/embriología , Gónadas/crecimiento & desarrollo , Proteínas del Helminto/fisiología , Humanos , Proteínas de Insectos/fisiología , Invertebrados/genética , Invertebrados/crecimiento & desarrollo , Larva , Masculino , Mamíferos/embriología , Mamíferos/genética , Mamíferos/crecimiento & desarrollo , Ratones , Oogénesis , ARN/metabolismo , ARN Helicasas/fisiología , Proteínas de Unión al ARN/fisiología , Vertebrados/genética , Vertebrados/crecimiento & desarrollo , Xenopus laevis/embriología , Xenopus laevis/crecimiento & desarrolloRESUMEN
Many RNAs involved in determination of the oocyte, specification of embryonic axes, and establishment of germ cells in Drosophila are localized asymmetrically within the developing egg or syncytial embryo. Here I review the current state of knowledge about the cis-acting sequences involved in RNA targeting, RNA binding proteins; gene activities implicated in localizing specific RNAs, and the role of the tubulin and actin cytoskeletons in RNA sorting within the oocyte. Targeted RNAs are often under complex translational control, and the translational control of two RNAs that localize to the posterior of the oocyte, oskar and nanos, is also discussed. Prospects for filling gaps in our knowledge about the mechanisms of localizing RNAs and the importance of RNA sorting in regulating gene expression are also explored.
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Drosophila/genética , Oocitos/metabolismo , ARN/metabolismo , Animales , Transporte Biológico , Drosophila/embriología , Regulación de la Expresión Génica , Proteínas de Unión al ARN/metabolismoRESUMEN
Sam68 is a member of a growing family of RNA-binding proteins that contains an extended K homology (KH) domain embedded in a larger domain called the GSG (GRP33, Sam68, GLD1) domain. To identify GSG domain family members, we searched data bases for expressed sequence tags encoding related portions of the Sam68 KH domain. Here we report the identification of two novel Drosophila KH domain proteins, which we termed KEP1 (KH encompassing protein) and SAM. SAM bears sequence identity with mammalian Sam68 and may be the Drosophila Sam68 homolog. We demonstrate that SAM, KEP1, and the recently identified Drosophila Who/How are RNA-binding proteins that are able to self-associate into homomultimers. The GSG domain of KEP1 and SAM was necessary to mediate the RNA binding and self-association. To elucidate the cellular roles of these proteins, SAM, KEP1, and Who/How were expressed in mammalian and Drosophila S2 cells. KEP1 and Who/How were nuclear and SAM was cytoplasmic. The expression of KEP1 and SAM, but not Who/How, activated apoptotic pathways in Drosophila S2 cells. The identification of KEP1 and SAM implies that a large GSG domain protein family exists and helps redefine the boundaries of the GSG domain. Taken together, our data suggest that KEP1 and SAM may play a role in the activation or regulation of apoptosis and further implicate the GSG domain in RNA binding and oligomerization.
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Proteínas de Unión al ARN/metabolismo , Familia-src Quinasas/metabolismo , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Apoptosis , Línea Celular , Clonación Molecular , Drosophila , Datos de Secuencia Molecular , Alineación de Secuencia , TransfecciónRESUMEN
Bicaudal-C (Bic-C) is required during Drosophila melanogaster oogenesis for several processes, including anterior-posterior patterning. The gene encodes a protein with five copies of the KH domain, a motif found in a number of RNA-binding proteins. Using antibodies raised against the BIC-C protein, we show that multiple isoforms of the protein exist in ovaries and that the protein, like the RNA, accumulates in the developing oocyte early in oogenesis. BIC-C protein expressed in mammalian cells can bind RNA in vitro, and a point mutation in one of the KH domains that causes a strong Bic-C phenotype weakens this binding. In addition, oskar translation commences prior to posterior localization of oskar RNA in Bic-C- oocytes, indicating that Bic-C may regulate oskar translation during oogenesis.
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Proteínas de Drosophila , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Biosíntesis de Proteínas , Proteínas de Unión al ARN/metabolismo , Alelos , Animales , Arginina/genética , Arginina/metabolismo , Células COS , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Glicina/genética , Glicina/metabolismo , Mutagénesis Sitio-Dirigida , Oocitos , Oogénesis , ARN/metabolismo , Proteínas de Unión al ARN/genética , Cloruro de SodioRESUMEN
The Drosophila gene vasa is required for pole plasm assembly and function, and also for completion of oogenesis. To investigate the role of vasa in oocyte development, we generated a new null mutation of vasa, which deletes the entire coding region. Analysis of vasa-null ovaries revealed that the gene is involved in the growth of germline cysts. In vasa-null ovaries, germaria are atrophied, and contain far fewer developing cysts than do wild-type germaria; a phenotype similar to, but less severe than, that of a null nanos allele. The null mutant also revealed roles for vasa in oocyte differentiation, anterior-posterior egg chamber patterning, and dorsal-ventral follicle patterning, in addition to its better-characterized functions in posterior embryonic patterning and pole cell specification. The anterior-posterior and dorsal-ventral patterning phenotypes resemble those observed in gurken mutants. vasa-null oocytes fail to efficiently accumulate many localized RNAs, such as Bicaudal-D, orb, oskar, and nanos, but still accumulate gurken RNA. However, GRK accumulation in the oocyte is severely reduced in the absence of vasa function, suggesting a function for VASA in activating gurken translation in wild-type ovaries.
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Proteínas de Drosophila , Drosophila/citología , Proteínas de Insectos/biosíntesis , Oogénesis/fisiología , Quistes Ováricos/genética , ARN Helicasas , ARN Nucleotidiltransferasas/fisiología , Factor de Crecimiento Transformador alfa , Factores de Crecimiento Transformadores/biosíntesis , Animales , Secuencia de Bases , Tipificación del Cuerpo , Diferenciación Celular , Citoplasma/química , ARN Helicasas DEAD-box , Femenino , Proteínas de Insectos/análisis , Proteínas de Insectos/genética , Datos de Secuencia Molecular , Oocitos/química , Oocitos/citología , Oocitos/metabolismo , ARN Nucleotidiltransferasas/genética , ARN Mensajero/análisis , Eliminación de Secuencia , Factores de Crecimiento Transformadores/genéticaRESUMEN
Sam68 is a member of a growing family of proteins that contain a single KH domain embedded in a larger conserved domain of approximately 170 amino acids. Loops 1 and 4 of this KH domain family are longer than the corresponding loops in other KH domains and contain conserved residues. KH domains are protein motifs that are involved in RNA binding and are often present in multiple copies. Here we demonstrate by coimmunoprecipitation studies that Sam68 self-associated and that cellular RNA was required for the association. Deletion studies demonstrated that the Sam68 KH domain loops 1 and 4 were required for self-association. The Sam68 interaction was also observed in Saccharomyces cerevisiae by the two-hybrid system. In situ chemical cross-linking studies in mammalian cells demonstrated that Sam68 oligomerized in vivo. These Sam68 complexes bound homopolymeric RNA and the SH3 domains of p59fyn and phospholipase Cgamma1 in vitro, demonstrating that Sam68 associates with RNA and signaling molecules as a multimer. The formation of the Sam68 complex was inhibited by p59fyn, suggesting that tyrosine phosphorylation regulates Sam68 oligomerization. Other Sam68 family members including Artemia salina GRP33, Caenorhabditis elegans GLD-1, and mouse Qk1 also oligomerized. In addition, Sam68, GRP33, GLD-1, and Qk1 associated with other KH domain proteins such as Bicaudal C. These observations indicate that the single KH domain found in the Sam68 family, in addition to mediating protein-RNA interactions, mediates protein-protein interactions.
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Proteínas de Caenorhabditis elegans , Proteínas de Unión al ADN/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Homología de Secuencia de Aminoácido , Proteínas Adaptadoras Transductoras de Señales , Animales , Proteínas de Unión al ADN/genética , Dimerización , Células HeLa , Proteínas del Helminto/metabolismo , Humanos , Proteínas de Insectos/metabolismo , Ratones , Fosfoproteínas/genética , Mutación Puntual , Poli U/metabolismo , Pruebas de Precipitina , Unión Proteica , Conformación Proteica , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-fyn , ARN/fisiología , Proteínas de Unión al ARN/genética , Proteínas Recombinantes de FusiónRESUMEN
oskar (osk) mRNA is tightly localized to the posterior pole of the Drosophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced expression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localization process, ensuring that Osk protein is only expressed after the mRNA has reached the posterior. An ovarian protein, Bruno (Bru), has been implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the expression cloning of an RNA-binding protein, and the identification of previously described mutants in the arrest (aret)-locus as mutants in Bru. The mutant phenotype, along with the binding properties of the protein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesis as well as early in embryogenesis. Genetic experiments provide further evidence that Bru functions in the translational repression of osk. Intriguingly, we find that Bru interacts physically with Vasa (Vas), an RNA helicase that is a positive regulator of osk translation. Bru belongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for the molecular mechanism of Bru function are discussed.
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Proteínas de Drosophila , Drosophila/genética , Biosíntesis de Proteínas/genética , ARN Helicasas , Proteínas de Unión al ARN/metabolismo , Proteínas Represoras/metabolismo , Factor de Crecimiento Transformador alfa , Secuencia de Aminoácidos , Animales , Clonación Molecular , Secuencia Conservada/genética , ARN Helicasas DEAD-box , Drosophila/embriología , Drosophila/crecimiento & desarrollo , Evolución Molecular , Femenino , Regulación de la Expresión Génica/genética , Genes de Insecto , Proteínas de Insectos/genética , Masculino , Datos de Secuencia Molecular , Mutación/genética , Oogénesis/genética , Fenotipo , ARN Nucleotidiltransferasas/genética , ARN Nucleotidiltransferasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas Represoras/genética , Alineación de Secuencia , Factores de Crecimiento Transformadores/genéticaRESUMEN
In Drosophila melanogaster, position-effect variegation of the white gene has been a useful phenomenon by which to study chromosome structure and the genes that modify it. We have identified a new enhancer of variegation locus, Dmrnahel (hel). Deletion of mutation of hel enhances white variegation, and this can be reversed by a transformed copy of hel+. In the presence of two endogenous copies, the transformed hel+ behaves as a suppressor of variegation. hel is an essential gene and functions both maternally and zygotically. The HEL protein is similar to known RNA helicases, but contains an unusual variant (DECD) of the DEAD motif common to these proteins. Potential HEL homologues have been found in mammals, yeast and worms. HEL protein associates with salivary gland chromosomes and locates to nuclei of embryos and ovaries, but disappears in mitotic domains of embryos as chromosomes condense. We propose that the HEL protein promotes an open chromatin structure that favors transcription during development by regulating the spread of heterochromatin, and that HEL is regulated by, and may have a role in, the mitotic cell cycle during embryogenesis.