A retrocopy of a gene can functionally displace the source gene in evolution

The e(y)2 gene of Drosophila melanogaster encodes the ubiquitous evolutionarily conserved co-activator of RNA polymerase II that is involved in transcription regulation of a high number of genes. The Drosophila e(y)2b gene, paralogue of the e(y)2 has been found. The analysis of structure of the e(y)2, e(y)2b and its orthologues from other species reveals that the e(y)2 gene derived as a result of retroposition of the e(y)2b during Drosophila evolution. The mRNA-derived retrogenes lack introns or regulatory regions; most of them become pseudogenes whereas some acquire tissue-specific functions. Here we describe the different situation: the e(y)2 retrogene performs the general function and is ubiquitously expressed, while the source gene is functional only in a small group of male germ cells. This must have resulted from retroposition into a transcriptionally favorable region of the genome

DEVELOPMENT OF PROVISIONS FOR EVALUATING THE EFFECTIVENESS OF URBAN PUBLIC PASSENGER TRANSPORT SYSTEM

The work presents a methodology that allows us to evaluate the effectiveness of the system in accordance with accepted standards in terms of the three components of the “passenger–carrier–department” system, taking into account the interests of each side. The given comprehensive effectiveness evaluation of the urban public passenger transport system shows that a new scientific idea consists in forming fundamentally new sets of indicators for each participant of the system (passenger–carrier–department of transport) that correspond to the conditions of functioning of the urban passenger transport system in Russian Federation. The article presents a classification model for the formation of a basic system of indicators and a functional scheme for grouping and ranking them. The effectiveness of the urban public passenger transport system can be considered separately for each participant in the system from its side, in two directions: horizontal (by year, for example, for an enterprise) and vertical (in the current period for all participants)

Use of computer support as motivation for studying language information units for carrying out professional maritime activities in communication conditions

The relevance of studying English marine terminology is due to work with original materials as part of professional activities in negotiating with coast stations, port authorities and various services of foreign countries. One has to deal with a huge number of information units (IU) required in communication. The problem consists in a comparative consideration of the language terminological processes in professional maritime activities (PMA). The aim of the study is to motivate the study of language IU using computer support for the implementation of PMA in communication. The research methods include testing of experimental groups in training and control modes, using “STEP” computer training system; testing control groups using paper media. IMO standard phrases are the language basis of the test tasks. As a result of the scientific research the possibility of studying IU in a short period of time using a computer program in training and control modes has been presented. It has been experimentally revealed that computer support promotes the development of reflective personality traits through inducing self-assessment of the ability to rely on the IU studied and organizing one's own actions for their assimilation; comprehension and formation of one’s own attitude to IU and motivation for their study; forecasting mutual understanding in relations with a possible partner based on the material being studied; current self-organization of the sequence of actions of perception, reproduction and rethinking of IU and self-assessment of their assimilation. This leads to high motivation of the learning process in order to master professional activities

The role of SAGA in the transcription and export of mRNA

SAGA/TFTC, which is a histone acetyltransferase complex, plays an important role in the regulation of transcription. We have identified that the metazoan TFTC/STAGA complexes had histone H2A and H2B deubiquitinase activity that is carried out by a DUBm (deubiquitination module). We studied the DUBm of SAGA in Drosophila melanogaster and identified Drosophila homologs of yeast DUBm components. Two subunits of DUBm (Sus1/ENY2 and Sgf11) were shown to have functions separate from DUBm function. Thus, Sus1/ENY2 was shown to be present in several different complexes. Sgf11 was found to be associated with the cap-binding complex (CBC) and recruited onto growing messenger ribonucleic acid (mRNA). Also, we have shown that Sgf11 interacted with the TREX-2/AMEX mRNA export complex and was essential for mRNA export from the nucleus. Immunostaining of the polytene chromosomes of Drosophila larvae revealed that Sgf11 is present at the sites of localization of snRNA genes. It was also found in immunostaining experiments that dPbp45, the subunit of the PBP complex, the key player in the snRNA transcription process, is associated not only with the snRNA gene localization sites, but with other sites of active transcription by PolII. We also revealed that Sgf11 was present at many active transcription sites in interbands and puffs on polytene chromosomes, Sgf11 was localized at all Brf1 (the component of the RNA polymerase III basal transcription complex) sites. We concluded that SAGA coactivated transcription of both the PolII and PolIII-dependent snRNA genes

Диагностика сочетанной черепно-мозговой травмы, сопровождающейся шоком, с позиций системного подхода

Polytrauma has a number of the clinical features caused by system processes of pathogenesis of critical conditions. On the basis of experience of treatment of 553 patients with brain bruises with extracranial damages and accompanied by a traumatic shock, essentially new approach is developed by authors in diagnostics of this pathology, providing pathogenesis’ caused possibility of increase of severe craniocerebral trauma in the sharp period of traumatic illness.Сочетанная черепно-мозговая травма имеет ряд клинических особенностей, обусловленных системными процессами патогенеза критических состояний. На основании опыта лечения 553 пострадавших с ушибами головного мозга, сочетанными с внечерепными повреждениями и сопровождающимися травматическим шоком, выработан принципиально новый подход к диагностике данной патологии, предусматривающий обусловленную патогенетически возможность нарастания тяжести черепно-мозговой травмы в остром периоде травматической болезни

Sem1 is a functional component of the nuclear pore complex–associated messenger RNA export machinery

The evolutionarily conserved protein Sem1/Dss1 is a subunit of the regulatory particle (RP) of the proteasome, and, in mammalian cells, binds the tumor suppressor protein BRCA2. Here, we describe a new function for yeast Sem1. We show that sem1 mutants are impaired in messenger RNA (mRNA) export and transcription elongation, and induce strong transcription-associated hyper-recombination phenotypes. Importantly, Sem1, independent of the RP, is functionally linked to the mRNA export pathway. Biochemical analyses revealed that, in addition to the RP, Sem1 coenriches with components of two other multisubunit complexes: the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation. Notably, targeting of Thp1, a TREX-2 component, to the NPC is perturbed in a sem1 mutant. These findings reveal an unexpected nonproteasomal function of Sem1 in mRNA export and in prevention of transcription-associated genome instability. Thus, Sem1 is a versatile protein that might stabilize multiple protein complexes involved in diverse pathways.España, Ministerio de Educación y Ciencia BFU2006-05260 and BFU2007-28647Andalucia, Junta de Andalucia CVI102 and CVI254

Genome-wide studies of the multi-zinc finger Drosophila Suppressor of Hairy-wing protein in the ovary

The Drosophila Suppressor of Hairy-wing [Su(Hw)] protein is a globally expressed, multi-zinc finger (ZnF) DNA-binding protein. Su(Hw) forms a classic insulator when bound to the gypsy retrotransposon and is essential for female germline development. These functions are genetically separable, as exemplified by Su(Hw)f that carries a defective ZnF10, causing a loss of insulator but not germline function. Here, we completed the first genome-wide analysis of Su(Hw)-binding sites (SBSs) in the ovary, showing that tissue-specific binding is not responsible for the restricted developmental requirements for Su(Hw). Mapping of ovary Su(Hw)f SBSs revealed that female fertility requires binding to only one third of the wild-type sites. We demonstrate that Su(Hw)f retention correlates with binding site affinity and partnership with Modifier of (mdg4) 67.2 protein. Finally, we identify clusters of co-regulated ovary genes flanked by Su(Hw)f bound sites and show that loss of Su(Hw) has limited effects on transcription of these genes. These data imply that the fertility function of Su(Hw) may not depend upon the demarcation of transcriptional domains. Our studies establish a framework for understanding the germline Su(Hw) function and provide insights into how chromatin occupancy is achieved by multi-ZnF proteins, the most common transcription factor class in metazoans

Context Differences Reveal Insulator and Activator Functions of a Su(Hw) Binding Region

Insulators are DNA elements that divide chromosomes into independent transcriptional domains. The Drosophila genome contains hundreds of binding sites for the Suppressor of Hairy-wing [Su(Hw)] insulator protein, corresponding to locations of the retroviral gypsy insulator and non-gypsy binding regions (BRs). The first non-gypsy BR identified, 1A-2, resides in cytological region 1A. Using a quantitative transgene system, we show that 1A-2 is a composite insulator containing enhancer blocking and facilitator elements. We discovered that 1A-2 separates the yellow (y) gene from a previously unannotated, non-coding RNA gene, named yar for y-achaete (ac) intergenic RNA. The role of 1A-2 was elucidated using homologous recombination to excise these sequences from the natural location, representing the first deletion of any Su(Hw) BR in the genome. Loss of 1A-2 reduced yar RNA accumulation, without affecting mRNA levels from the neighboring y and ac genes. These data indicate that within the 1A region, 1A-2 acts an activator of yar transcription. Taken together, these studies reveal that the properties of 1A-2 are context-dependent, as this element has both insulator and enhancer activities. These findings imply that the function of non-gypsy Su(Hw) BRs depends on the genomic environment, predicting that Su(Hw) BRs represent a diverse collection of genomic regulatory elements

Altered Chromosomal Positioning, Compaction, and Gene Expression with a Lamin A/C Gene Mutation

Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression.To investigate the hypothesis that mutant lamin A/C changes the lamina's ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction.These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered

Comparative genomics of proteins involved in RNA nucleocytoplasmic export

Background: The establishment of the nuclear membrane resulted in the physical separation of transcription and translation, and presented early eukaryotes with a formidable challenge: how to shuttle RNA from the nucleus to the locus of protein synthesis. In prokaryotes, mRNA is translated as it is being synthesized, whereas in eukaryotes mRNA is synthesized and processed in the nucleus, and it is then exported to the cytoplasm. In metazoa and fungi, the different RNA species are exported from the nucleus by specialized pathways. For example, tRNA is exported by exportin-t in a RanGTP-dependent fashion. By contrast, mRNAs are associated to ribonucleoproteins (RNPs) and exported by an essential shuttling complex (TAP-p15 in human, Mex67-mtr2 in yeast) that transports them through the nuclear pore. The different RNA export pathways appear to be well conserved among members of Opisthokonta, the eukaryotic supergroup that includes Fungi and Metazoa. However, it is not known whether RNA export in the other eukaryotic supergroups follows the same export routes as in opisthokonts. Methods: Our objective was to reconstruct the evolutionary history of the different RNA export pathways across eukaryotes. To do so, we screened an array of eukaryotic genomes for the presence of homologs of the proteins involved in RNA export in Metazoa and Fungi, using human and yeast proteins as queries. Results: Our genomic comparisons indicate that the basic components of the RanGTP-dependent RNA pathways are conserved across eukaryotes, and thus we infer that these are traceable to the last eukaryotic common ancestor (LECA). On the other hand, several of the proteins involved in RanGTP-independent mRNA export pathways are less conserved, which would suggest that they represent innovations that appeared later in the evolution of eukaryotes. Conclusions: Our analyses suggest that the LECA possessed the basic components of the different RNA export mechanisms found today in opisthokonts, and that these mechanisms became more specialized throughout eukaryotic evolution