Vol 88, No 6 (2023)

The study of aminoglycoside acetyltransferases in actinobacteria of the genus Streptomyces is an integral part of the study of soil bacteria as the main reservoir and possible source of drug resistance genes. Previously, in the strain Streptomyces rimosus ATCC 10970 (producing oxyteteracycline), which is resistant to most natural aminoglycoside antibiotics, we have identified and biochemically characterized 3 aminoglycoside phosphotransferases, which cause resistance to kanamycin, neomycin, paromomycin, streptomycin, and hygromycin B. In the presented work, it was shown that resistance to other AGs in this strain is associated with the presence of the enzyme aminoglycoside acetyltransferase, belonging to the AAC(2′) subfamily. Induction of the expression of the gene, designated by us as aac(2′)-If, in Escherichia coli cells determines resistance to a wide range of natural aminoglycoside antibiotics (neomycin, gentamicin, tobramycin, sisomycin, and paromomycin) and to an increase in the minimum inhibitory concentrations of these antibiotics.

The impact of hypoxia causes changes in the transcription of genes that contribute to the adaptation of cells to a lack of oxygen. The main mechanism regulating the cellular response to hypoxia is the activation of a group of transcription factors of the HIF (Hypoxia-Inducible Factor) family, which include several isoforms and control the expression of more than a thousand genes. HIF activity is regulated at various levels, including by small non-coding RNA molecules called microRNAs (miRNAs). miRNAs regulate the cellular response to hypoxia by influencing the activation of HIF, its degradation, and the translation of proteins dependent on it. At the same time, HIF also affects miRNA biogenesis. Data on the relationship of a particular HIF isoform with miRNA are contradictory, since studies are performed using different cell lines, different types of experimental animals and clinical material, as well as at different oxygen concentrations and different durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which is not taken into account in studies. This review analyzes data on the effect of hypoxia on the biogenesis and functioning of miRNAs, as well as the effect of microRNAs on mRNAs of genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of the relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.

The blue-light sensors cryptochromes compose the widespread class of flavoprotein photoreceptors, regulating in plants signaling processes underlying their development, growth, and metabolism. In several algae cryptochromes may act not only as sensory photoreceptors but also as photolyases, catalyzing the repair of UV-induced DNA lesions. Cryptochromes bind FAD as the chromophore in the photolyase homologous region (PHR) domain and contain the cryptochrome C-terminal extension (CCE), which lacks in photolyases. Photosensory process in cryptochrome is initiated by photochemical chromophore conversions, including the formation of FAD redox forms. In a state with the chromophore reduced to neutral radical (FADH^•), photoreceptory protein undergoes phosphorylation, conformational changes, and disengagement of the PHR domain and CCE with the subsequent formation of oligomers of cryptochrome molecules. Photooligomerization is a structural basis of functional activity of cryptochromes, which determines the formation of their complexes with variety of signaling proteins, including transcriptional factors and transcription regulators. Interactions in such complexes change the protein signaling activity, leading to gene expression regulation and plant photomorphogenesis. In recent years, multiple papers, reporting novel, more detailed information about molecular mechanisms of above-mentioned processes were published. The present review largely focuses on the analysis of data contained in these publications, particularly regarding structural aspects of cryptochrome transitions into photoactivated states and regulatory signaling processes mediated by cryptochrome photoreceptors in plants.

Interplane (stacking) interactions of heterocyclic bases of nucleotide residues (n.t.) of RNA are one of the most important factors in the organization of its secondary and tertiary structure. Most of these (canonical) interactions are carried out between neighbors in the polynucleotide chains of RNA. However, with the accumulation of data on the atomic tertiary structures of a wide variety of RNAs and their complexes with proteins, it became clear that RNA nucleotide residues that are not neighbors in their polynucleotide chains and are sometimes separated in the RNA primary structure by tens or hundreds of n.t. can interact with the help of base stacking (non-canonical). This paper presents an exhaustive database of such elements and their environment in the macromolecules of natural and synthetic RNAs. They were called nonadjacent base-stacking elements (NA-BSE). The analysis of these data showed that the NA-BSE forming nucleotides, on average, account for about a quarter of all nucleotides of a particular RNA, therefore, they should be considered as real motifs in their tertiary structure. The classification of NA-BSE by types of localization in RNA macromolecules is carried out. It is shown that the structure-forming role of NA-BSE consists in the compact folding of single-stranded RNA loops, in the transformation of double-stranded bulges into imperfect helices, as well as in the binding of RNA regions removed in their primary and secondary structure.

Normalization of secretory activity and the level of differentiation of mesenchymal cells, including fibroblasts, is the important biomedical problem. One of the plausible solutions to this problem is to affect the unfolded protein response (UPR) signaling cascade, which is activated during fibroblast differentiation. In the present study, the effect of phytohormones on the secretory activity and differentiation of cultured human dermal fibroblasts was investigated. By analyzing the expression level of genes encoding UPR markers in these cells, we found that phytohormone abscisic acid (ABA) upregulated the expression of GRP78 and ATF4 genes, while phytohormone gibberellic acid (GA) upregulated the expression of CHOP. Evaluation of the biosynthetic activity of fibroblasts showed that ABA elevated the level of secretion and synthesis of procollagen I and the level of fibronectin synthesis, as well as total production of collagen and non-collagen proteins of extracellular matrix. ABA also stimulated the synthesis of smooth muscle actin α (α-SMA) and increased the number of myofibroblasts in cell population. On the contrary, GA increased the level of fibronectin secretion, but decreased the level of procollagen I synthesis, and reduced the total production of collagen proteins of extracellular matrix. Concomitantly, in these conditions we observed the decreased level of α-SMA synthesis and the number of myofibroblasts in the cell population. Our results suggest that phytohormones are the modulators of the biosynthetic activity of fibroblasts and affect their differentiation status.

Discovery of Thiomargarita magnifica - an exceptionally large giant sulfur bacterium - urges us to pay additional attention to the giant sulfur bacteria and to revisit our recent bioinformatic finding of lipoxygenases in the representatives of the genus Beggiatoa. These close relatives of Thiomargarita magnifica meet the similar size requirements by forming multicellular structures. We hypothesize that their lipoxygenases are a part of the oxylipin signaling system that provides high level of cell-to-cell signaling complexity which, in turn, enables them to reach large sizes.

Василий Николаевич Попов был выдающимся учёным и талантливым организатором науки и образования. Его ранняя смерть в возрасте 48 лет стала невосполнимой утратой. Он известен научному сообществу своими работами по биоэнергетике митохондрий у растений и животных, биохимии старения, биохимической генетике рака, нейробиологии.