Comparative analysis of orthologous eukaryotic mRNAs: potential hidden functional signals

Sequencing of multiple, nearly complete eukaryotic genomes creates opportunities for detecting previously unnoticed, subtle functional signals in non-coding regions. A genome-wide comparative analysis of orthologous sets of mammalian and yeast mRNAs revealed distinct patterns of evolutionary conservation at the boundaries of the untranslated regions (UTRs) and the coding region (CDS). Elevated sequence conservation was detected in ~30 nt regions around the start codon. There seems to be a complementary relationship between sequence conservation in the ~30 nt regions of the 5′-UTR immediately upstream of the start codon and that in the synonymous positions of the 5′-terminal 30 nt of the CDS: in mammalian mRNAs, the 5′-UTR shows a greater conservation than the CDS, whereas the opposite trend holds for yeast mRNAs. Unexpectedly, a ~30 nt region downstream of the stop codon shows a substantially lower level of sequence conservation than the downstream portions of the 3′-UTRs. However, the sequence in this poorly conserved 30 nt portion of the 3′-UTR is non-random in that it has a higher GC content than the rest of the UTR. It is hypothesized that the elevated sequence conservation in the region immediately upstream of the start codon is related to the requirement for initiation factor binding during pre-initiation ribosomal scanning. In contrast, the poorly conserved region downstream of the stop codon could be involved in the post- termination scanning and dissociation of the ribosomes from the mRNA, which requires only the mRNA–ribosome interaction. Additionally, it was found that the choice of the stop codon in mammals, but not in yeasts, and the context in the immediate vicinity of the stop codons in both mammals and yeasts are subject to strong selection. Thus, genome-wide analysis of orthologous gene sets allows detection of previously unrecognized patterns of sequence conservation, which are likely to reflect hidden functional signals, such as ribosomal filters that could regulate translation by modulating the interaction between the mRNA and ribosomes.     

Electroretinography in the diagnosis of thallium intoxication

Appearance of dystrophic alterations in the retina was carried out by administering 0.2 ml 12 mM of tallium chloride solution into the vitreous humour of 9 rabbits. Electroretinographic examination revealed a decline in the b wave either decreasing 2-3 times or entirely disappearing as early as on day 2 after the administration of tallium chloride. Electron microscopic investigation suggested that photoreceptors of the retina were initial by involved in the pathological process. Namely, the external segments of the photoreceptors were found to be reduced, indicating impairment of the formation of photoreceptor disks, which is known to proceed continuously under normal conditions. In the absence of an electroretinogram (ERG), the photoreceptor layers were shown to have disappeared completely. An examination of 28 subjects who were exposed to tallium and its compound at work revealed impaired retinal electrogenesis, as evident from subnormal ERG responses. This was of a functional nature and became more pronounced as occupational exposure time increased. The fact that the internal retinal layers and the 3-rd neurone remained intact, as suggested by the electrical sensitivity of the eye and lability of the optic nerve as well as by static perimetry, correlated with the EM findings obtained in experiments. Ophthalmobiomicroscopic examination of 12 eyes yielded data on characteristic changes in the lens when visual functions remained intact. These findings suggest that changes in the ERG may be indicative of initial preclinical symptoms of tallium intoxication and as such can be used when persons exposed to it in industry receive check-ups.     

Genetic polymorphism of poultry blood serum esterases in relation to resistance to bacterial infections

The experiments were carried out on White Leghorn, White Rock and Cornish chickens during the 1974--1975 season. The aim of the investigation was to study polymorphism of blood esterases in chickens in relation to their resistance to Salmonella pullorum and S. gallinarum. The data obtained indicate the following: 1) an additional, inheritant alyesterase fraction (A1) Appears in blood serum of resistant chickens after their contamination with Salmonella; 2) most chickens, which are resistant to Salmonella, have heterozygous genotype for blood serum cholinesterase.     

Uncoupling proteins: a role in protection against reactive oxygen species--or not?

A physiological function of the original uncoupling protein, UCP1, is well established: UCP1 is the molecular background for nonshivering thermogenesis. The functions of the "novel" UCPs, UCP2 and UCP3, are still not established. Recent discussions imply that all UCPs may play a role in protection against reactive oxygen species (ROS). Here we examine critically the evidence that UCP1, UCP2 and UCP3 are stimulated by ROS (superoxide) or ROS products (4-hydroxy-2-nonenal), and that the UCPs actually diminish oxidative damage. We conclude that, concerning UCP1, it is unlikely that it has such a role; concerning UCP2/UCP3, most evidence for physiologically significant roles in this respect is still circumstantial.     

Computational models with thermodynamic and composition features improve siRNA design

Background  

Small interfering RNAs (siRNAs) have become an important tool in cell and molecular biology. Reliable design of siRNA molecules is essential for the needs of large functional genomics projects.     

Abundance of type I toxin–antitoxin systems in bacteria: searches for new candidates and discovery of novel families

Small, hydrophobic proteins whose synthesis is repressed by small RNAs (sRNAs), denoted type I toxin–antitoxin modules, were first discovered on plasmids where they regulate plasmid stability, but were subsequently found on a few bacterial chromosomes. We used exhaustive PSI-BLAST and TBLASTN searches across 774 bacterial genomes to identify homologs of known type I toxins. These searches substantially expanded the collection of predicted type I toxins, revealed homology of the Ldr and Fst toxins, and suggested that type I toxin–antitoxin loci are not spread by horizontal gene transfer. To discover novel type I toxin–antitoxin systems, we developed a set of search parameters based on characteristics of known loci including the presence of tandem repeats and clusters of charged and bulky amino acids at the C-termini of short proteins containing predicted transmembrane regions. We detected sRNAs for three predicted toxins from enterohemorrhagic Escherichia coli and Bacillus subtilis, and showed that two of the respective proteins indeed are toxic when overexpressed. We also demonstrated that the local free-energy minima of RNA folding can be used to detect the positions of the sRNA genes. Our results suggest that type I toxin–antitoxin modules are much more widely distributed among bacteria than previously appreciated.     

Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants

Cellular and Molecular Neurobiology - The opioid receptor (OPR) family comprises the mu-, delta-, and kappa-opioid, and nociceptin receptors that belong to the superfamily of 7-transmembrane...