ABSTRACT
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level in the cytoplasm and play an important role in a wide range of biological processes. Recent studies have found that the miRNA sequences are presented not only in the cytoplasm, but also in the mitochondria. These miRNAs (the so-called mitomiRs) may be the sequences of nuclear or mitochondrial origin; some of them are involved in regulation of the mitochondrial gene functions, while the role of others is still unknown. The identification of nucleotide signals, which are unique to mitomiRs, may help to determine this role. We formed a dataset that combined the experimentally discovered mitomiRs in human, rat and mouse. To isolate signals that may be responsible for the mitomiRs' functions or for their translocation from or into mitochondria a context analysis was carried out for the sequences. For three species in the group mitomiRs/non-mitomiRs and the group of all miRNAs from the miRBase database statistically overrepresented 8-letter motifs were identified (p-value < 0.01 with Bonferroni correction for multiple comparisons), for these motifs the patterns of the localization in functionally important regions for different types of miRNAs were found. Also, for the group mitomiRs/non-mitomiRs we found the statistically significant features of the miRNA nucleotide context near the Dicer and Drosha cleavage sites (Pearson's χ2 test of independence for the first three positions of the miRNA, p-value < 0.05). The observed nucleotide frequencies may indicate a more homogeneous pri-miRNA cleavage by the Drosha complex during the formation of the 5' end of mitomiRs. The obtained results can help to determine the role of the nucleotide signals in the origin, processing, and functions of the mitomiRs.
ABSTRACT
Many scientific articles became available in the digital form which allows for querying articles data, and specifically the automated metadata gathering, which includes the affiliation data. This in turn can be used in the quantitative characterization of the scientific field, such as organizations identification, and analysis of the co-authorship graph of those organizations to extract the underlying structure of science. In our work, we focus on the miRNA science field, building the organization co-authorship network to provide the higher-level analysis of scientific community evolution rather than analyzing author-level characteristics. To tackle the problem of the institution name writing variability, we proposed the k-mer/n-gram boolean feature vector sorting algorithm, KOFER in short. This approach utilizes the fact that the contents of the affiliation are rather consistent for the same organization, and to account for writing errors and other organization name variations within the affiliation metadata field, it converts the organization mention within the affiliation to the K-Mer (n-gram) Boolean presence vector. Those vectors for all affiliations in the dataset are further lexicographically sorted, forming groups of organization mentions. With that approach, we clustered the miRNA field affiliation dataset and extracted unique organization names, which allowed us to build the co-authorship graph on the organization level. Using this graph, we show that the growth of the miRNA field is governed by the small-world architecture of the scientific institution network and experiences power-law growth with exponent 2.64 ± 0.23 for organization number, in accordance with network diameter, proposing the growth model for emerging scientific fields. The first miRNA publication rate of an organization interacting with already publishing organization is estimated as 0.184 ± 0.002 year-1.
ABSTRACT
A microRNA (miRNA) is a small noncoding RNA molecule about 22 nucleotides in length. The paper describes a web server for predicting miRNAs and their precursors and binding sites. The predictions are based on either sequence similarity to known miRNAs of 223 organisms or context-structural hidden Markov models. It has been shown that the proposed methods of prediction of human miRNAs and pre-miRNAs outperform the existing ones in accuracy. The average deviation of predicted 5'-ends of human miRNAs from actual positions is 3.13 nt in the case of predicting one pair of complementary miRNAs (miRNA-miRNA* duplex). A useful option for our application is the prediction of an additional miRNA pair. In this mode, the pairs closest to actual miRNA deviate by 1.61 nt on average. The proposed method also shows good performance in predicting mouse miRNAs. Binding sites for miRNAs are predicted by two known approaches based on complementarity and thermodynamic stability of the miRNA-mRNA duplex and on a new approach, which takes into account miRNAs competition for the site. The role of the secondary structure in miRNA processing is considered. The web server is available at http://wwwmgs.bionet.nsc.ru/mgs/programs/rnaanalys/.
Subject(s)
MicroRNAs/chemistry , RNA Precursors/chemistry , RNA, Messenger/chemistry , Software , Animals , Base Pairing , Binding Sites , Binding, Competitive , Humans , Internet , Markov Chains , Nucleic Acid Conformation , RNA Stability , ThermodynamicsABSTRACT
The condition was studied of the pulmonary surfactant system in those patients with the syndrome of acute lung injury who had been placed on a partial emulsion ventilation of the lungs. The study of the surface tension of the endobronchial washings was made with the aid of the modified Willihelm balance before the start of the treatment and at post-treatment day 4, 6 and 8. The initial level of surface tension has been found out to be increased by 8.9%. The controlled indices were gradually returning to normal in the wake of the emulsion ventilation of the lungs. Partial emulsion ventilation of the lungs with perftoran makes for a prompt and complete restoration of surface activity of the pulmonary surfactant within 7 days. We consider it essential that a conventional intensive therapy of the acute lung injury syndrome be supplemented by partial emulsion ventilation of the lungs with perftoran.
Subject(s)
Fluorocarbons/pharmacology , Pulmonary Surfactants/drug effects , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Bronchoalveolar Lavage Fluid , Emulsions , Humans , Pulmonary Surfactants/physiology , Surface Tension , SyndromeABSTRACT
Computer system mRNA-FAST (mRNA--Function, Activity, STructure; http://wwwmgs.bionet.nsc.ru/mgs/dbases/trsig/) is described. The system has been developed to analyze nucleotide sequences of mRNA and to measure their essential properties. The system compiles the data base on translation signals including nucleotide sequences of the regulatory regions with structural and experimental information on their specific activities. It also contains programs to search for local homology between mRNA and translation signals, to search for potential signals basing on analysis of the oligonucleotide dictionaries, and to model secondary RNA structure. Possible applications of the system mRNA-FAST are discussed.
Subject(s)
Databases, Nucleic Acid , Nucleic Acid Conformation , RNA, Messenger/genetics , Base Sequence , Gene Expression Regulation , Molecular Sequence Data , RNA, Messenger/chemistry , Structure-Activity RelationshipABSTRACT
One of the main problems of metabolic engineering is to determine the genetically controlled limiting links of a metabolic network. We have built a model of the primary transport of inorganic phosphates (Pi), analyzed the Pi metabolic network in Gram-negative bacteria, and determined the factors controlling the phosphate exchange. The model explains why the Pi primary transport is not observed at the release stage. The nonlinearity of primary transport and the differences in its parameters in the membrane and within the cell give rise to transport asymmetry, i.e., the Pi release rate is low as compared with the uptake rate, and is small at the background of secondary transport. Discussed is a general scheme of coordination between primary and secondary transport, which are interconnected through the substrate-product reration.
Subject(s)
Bacteria/metabolism , Metabolism , Models, Biological , Phosphates/metabolism , Bacteria/genetics , Biological TransportABSTRACT
Signals of translation initiation of operons of Haemophilus influenzae ribosomal proteins were predicted. This process is regulated by the formation of secondary RNA structures to which one of the proteins encoded in a particular operon binds. In some cases, these structures imitate the region of protein binding to rRNA. Predictions are made by comparing with homologous operons of Escherichia coli and analogous regions of rRNA and by estimating the energy of secondary structure formation. It is shown that this regulatory mechanism occurs: in operons L11, S10, S15, spc, and alpha of H.influenzae and, probably, in operon S15 of Helicobacter pylori, Bacillus subtilis, and Mycoplasma genitalium.
