Irina L. Stepanenko

Transcription Regulatory Regions Database (TRRD): its status in 2002

Transcription Regulatory Regions Database (TRRD) is an informational resource containing an integrated description of the gene transcription regulation. An entry of the database corresponds to a gene and contains the data on localization and functions of the transcription regulatory regions as well as gene expression patterns. TRRD contains only experimental data that are inputted into the database through annotating scientific publication. TRRD release 6.0 comprises the information on 1167 genes, 5537 transcription factor binding sites, 1714 regulatory regions, 14 locus control regions and 5335 expression patterns obtained through annotating 3898 scientific papers. This information is arranged in seven databases: TRRDGENES (general gene description), TRRDLCR (locus control regions); TRRDUNITS (regulatory regions: promoters, enhancers, silencers, etc.), TRRDSITES (transcription factor binding sites), TRRDFACTORS (transcription factors), TRRDEXP (expression patterns) and TRRDBIB (experimental publications). Sequence Retrieval System (SRS) is used as a basic tool for navigating and searching TRRD and integrating it with external informational and software resources. The visualization tool, TRRD Viewer, provides the information representation in a form of maps of gene regulatory regions. The option allowing nucleotide sequences to be searched for according to their homology using BLAST is also included. TRRD is available at http://www.bionet.nsc.ru/trrd/.

GeneNet in 2005

The GeneNet system is designed for collection and analysis of the data on gene and metabolic networks, signal transduction pathways and kinetic characteristics of elementary processes. In the past 2 years, the GeneNet structure was considerably improved: (i) the current version of the database is now implemented using ORACLE9i; (ii) the capacities to describe the structure of the protein complexes and the interactions between the units are increased; (iii) two tables with kinetic constants and more detailed descriptions of certain reactions were added; and (iv) a module for kinetic modeling was supplemented. The current SRS release of the GeneNet database contains 37 graphical maps of gene networks, as well as descriptions of 1766 proteins, 1006 genes, 241 small molecules and 3254 relationships between gene network units, and 552 kinetic constants. Information distributed between 16 interlinked tables was obtained by annotating 1980 journal publications. SRS release of the GeneNet database, the graphical viewer and the modeling section are available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/.

GeneNet: a database on structure and functional organisation of gene networks.

The GeneNet database is designed for accumulation of information on gene networks. Original technology applied in GeneNet enables description of not only a gene network structure and functional relationships between components, but also metabolic and signal transduction pathways. Specialised software, GeneNet Viewer, automatically displays the graphical diagram of gene networks described in the database. Current release 3.0 of GeneNet database contains descriptions of 25 gene networks, 945 proteins, 567 genes, 151 other substances and 1364 relationships between components of gene networks. Information distributed between 14 interlinked tables was obtained by annotating 968 scientific publications. The SRS-version of GeneNet database is freely available (http://wwwmgs.bionet.nsc.ru/mgs/systems/genenet/).

Transcription Regulatory Regions Database (TRRD): A Source of Experimentally Confirmed Data on Transcription Regulatory Regions of Eukaryotic Genes

The goal of creation of the Transcription Regulatory Regions Database (TRRD) was to provide a complete and adequate description of the structure-function organization of transcription regulatory regions in eukaryotic genes. TRRD contains only experimentally confirmed data about (i) transcription factor binding sites; (ii) regulatory units (promoter regions, enhancers, and silencers); and (iii) locus control regions. The main tool for searching TRRD and navigation in it is SRS. TRRD has hierarchically organized vocabularies and thesauruses used for developing specialized data retrieval tools. The current TRRD release contains information about 2308 eukaryotic genes (of them, 34 % are human genes) inputted basing on annotation of 7565 scientific papers. For these genes, the largest in the world sets of experimentally confirmed regulatory units (3439) and transcription factor binding sites (10 045) are collected in TRRD. Of them, 37 % of regulatory units and 38 % of binding sites are related to human genes. This paper characterizes groups of experiments basing on which regulatory units and binding sites are annotated. Examples of TRRD entries are given. The database is available at http://www.bionet.nsc.ru/trrd/.

Heat Shock Proteins

Heat shock proteins (HSPs) are specific proteins that are made when cells are briefly exposed to temperatures above their normal growth temperature. The synthesis of HSPs is a universal phenomenon, occurring in all plant and animal species studied, including humans. HSPs are also made by prokaryotic cells, namely, bacterial and archaean. Because HSPs can also be induced by oxidants, toxins, heavy metals, free radicals, viruses, and other stressors, they are sometimes called the ‘stress proteins’. Most HSPs are molecular chaperones, which normally promote the self-assembly of newly synthesized polypeptide chains of proteins into a native spatial structure, the assembly of their complexes, and their transport through membranes as well as their participation in signal transduction. A nonlethal increase in temperature above the physiological norm for a biological species suppresses protein synthesis in the cell, activates the heat shock factor (HSF), and enhances transcription of heat shock genes, while exposure to a lethal temperature initiates apoptosis or programmed cell death. In turn, HSPs inhibit apoptosis and provide cells with thermal stability if stress reoccurs. In so doing, chaperones prevent irreversible aggregation of unfolded proteins and assist in the restoration of their native structure and/or degradation of denatured proteins. Response to heat shock is attenuated as the cell returns to normalcy after stress has been removed, HSF transforms to its inactive form and is transported to the cytoplasm, and ‘bookmarked preinitiation complexes’ are accumulated in the promoters of the genes encoding HSPs. HSP gene polymorphisms are associated with inflammatory, autoimmune, cardiovascular, and neurodegenerative diseases and, finally, aging.

Abundances of microRNAs in human cells can be estimated as a function of the abundances of YRHB and RHHK tetranucleotides in these microRNAs as an ill-posed inverse problem solution

Mature microRNAs (miRNAs) are small endogenous non-coding RNAs 18–25 nt in length. They program the RNA Induced Silencing Complex (RISC) to make it inhibit either messenger RNAs or promoter DNAs. We have found that the mean abundance of miRNAs in Arabidopsis is correlated with the abundance of DRYD tetranucleotides near the 3′-end and the abundance of WRHB tetranucleotides in the center of the miRNA sequence. Based on this correlation, we have estimated miRNA abundances in seven organs of this plant, namely: inflorescences, stems, siliques, seedlings, roots, cauline, and rosette leaves. We have also found that the mean affinity of miRNAs for two proteins in the Argonaute family (Ago2 and Ago3) in man is correlated with the abundance of YRHB tetranucleotides near the 3′-end and that the preference of miRNAs for Ago2 is correlated with the abundance of RHHK tetranucleotides in the center of the miRNA sequence. This allowed us to obtain statistically significant estimates of miRNA abundances in human embryonic kidney cells, HEK293T. These findings in relation to two taxonomically distant entities (man and Arabidopsis) fit one another like pieces of a jigsaw puzzle, which allowed us to heuristically generalize them and state that the miRNA abundance in the human brain may be determined by the abundance of YRHB and RHHK tetranucleotides in these miRNAs.

Argo_Viewer: A Package for Recognition and Analysis of Regulatory Elements in Eukaryotic Genes

The task of reliable recognition of promoters in eukaryotic genomes has not been yet solved completely. This is largely due to poor understanding of the features of the structure-function organization of eukaryotic promoters essential for their function and recognition. Five groups of promoters of tissue-specific genes were analyzed and vocabularies of region-specific oligonucleotide motifs were constructed. We suggest a procedure to recognize tissue-specific gene promoters basing on the presence and distribution of certain oligonucleotide motifs.

Transcription Regulatory Regions Database (TRRD): Description of Transcription Regulation and the Main Capabilities of the Database

The main goal of TRRD (http://www.bionet.nsc.ru/trrd/) construction is a complete and precise description of the structure—function organization of the regions of eukaryotic genes involved in transcription regulation. The current release of TRRD contains information on 2186 genes, 3254 regulatory units, 9480 transcription factor binding sites, 14 locus control regions, and 13 173 expression patterns. The data inputted into TRRD have been extracted from 7301 scientific papers. They are stored in seven SRS tables: TRRDGENES, TRRDUNITS, TRRDEXP, TRRDSITES, TRRDFACTORS, TRRDLCR, and TRRDBIB. The main tool for search of and navigation through TRRD is the Sequence Retrieval System (SRS). A hierarchical structure of dictionaries and thesauri has been developed to provide additional options for data retrieval.

Transcription regulation of eukaryotic genes: Description in the TRRdatabase

The structure of the Transcription Regulatory Regions Database (TRRD) and the principles of describing transcription regulation of eukaryotic genes in TRRD are considered. Formalized description of the structural and functional organization of the regulatory gene regions is illustrated with examples. By now, TRRD is based on 3500 original works and contains data on transcription regulation of more than 1100 genes known to possess more than 5000 transcription factor binding sites and about 1600 regulatory elements (promoters, enhancers, silencers). TRRD is available at http://www.bionet.nsc.ru/trrd/