Development Management of Interbank Competition in the Corporate Lending Market

Introduction. The effective functioning of the banking sector is a prerequisite for the economy development   and one of the main sources of providing monetary resources for economic activity of entrepreneurship, regardless of ownership forms and spheres of management. The urgent problem of business development today is the lack of own financial resources for economic activity and a significant reduction in corporate bank lending. Therefore, it is relevant to study and solve the problems of renewing lending by banks to the corporate sector at the present time, taking into account the prevention of the increase in the level of credit risk. Aim and tasks. The purpose of the study is to manage the development of interbank competition in the corporate lending market based on a study of the bank lending state to corporate clients and further prospects in the absence of an accurate forecast of the economic situation in Ukraine. Results. The analysis of the dynamics of the bank lending total volume to business in 2022-2023 and the structure of the provided corporate loans showed that since mid-2022 there has been a tendency to decrease the volume of loans to entrepreneurship, which is caused by a decrease in demand from borrowers and an increase in the cost of credit from banks. In addition, more than 70% of the loans provided are concentrated in five larger banks in Ukraine, including 4 state-owned ones, preferential lending to businesses with state support prevails. To further assess the development of corporate bank lending, a prediction of lending volumes for 2023 was carried out, which made it possible to establish that lending volumes by banks of non-financial corporations have a forecast downward trend. Conclusions.  Recommendations for improving corporate bank lending processes are proposed, namely: development of credit policy directions that will prevent a new crisis of confidence in banks and the banking system; development of measures that will prevent the curtailment of preferential targeted lending programs; developing measures to reduce the level of non-performing loans and solving the problem of lowering the cost of financing sources

Regulated dicing of pre-mir-144 via reshaping of its terminal loop.

Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2). We provide further evidence that this regulatory switch involves reshaping of the pre-mir-144 apical loop into a structure that is appropriate for Dicer cleavage. In light of our recent findings that mir-144 promotes the nuclear biogenesis of its neighbor mir-451, these data extend the complex hierarchy of nuclear and cytoplasmic regulatory events that can control the maturation of clustered miRNAs

Formation of Amyloid-Like Fibrils by Y-Box Binding Protein 1 (YB-1) Is Mediated by Its Cold Shock Domain and Modulated by Disordered Terminal Domains

YB-1, a multifunctional DNA- and RNA-binding nucleocytoplasmic protein, is involved in the majority of DNA- and mRNA-dependent events in the cell. It consists of three structurally different domains: its central cold shock domain has the structure of a β-barrel, while the flanking domains are predicted to be intrinsically disordered. Recently, we showed that YB-1 is capable of forming elongated fibrils under high ionic strength conditions. Here we report that it is the cold shock domain that is responsible for formation of YB-1 fibrils, while the terminal domains differentially modulate this process depending on salt conditions. We demonstrate that YB-1 fibrils have amyloid-like features, including affinity for specific dyes and a typical X-ray diffraction pattern, and that in contrast to most of amyloids, they disassemble under nearly physiological conditions

Mécanismes d'interaction YB-1/acides nucléiques et implications dans divers processus cellulaires

YB-1 est membre de la superfamille de protéines de choc thermique. YB-1 se lie à l'ARN et l'ADN. Des corrélations entre niveau élevé de YB-1, expression élevée de la P-glycoprotéine MDR1 et un mauvais pronostic ont été faites pour plusieurs types de cancer. Le rôle de YB-1 dans la cancérogenèse peut être soutenu par plusieurs mécanismes: i) l'activation de la transcription; ii) la participation à la réparation de l'ADN; iii) la régulation de la traduction. Les deux premiers modèles supposent une localisation nucléaire de YB-1, et cela malgré le fait que YB-1 est apparaît principalement dans cytoplasme dans des conditions physiologiques et les mécanismes de son accumulation nucléaire restent obscurs. Dans ce travail, nous avons tenté d’identifier les mécanismes qui déclenchent la translocation nucléaire de YB-1. Il est apparu que cette localisation nucléaire dépend principalement du niveau d’ARNm dans le cytoplasme et ainsi d’une transcription active, plutôt que de la présence de lésion à l'ADN nucléaire. A l'inverse, le rôle de YB-1 comme régulateur de la traduction est clairement établi. YB-1 peut influencer la traduction et favoriser la progression du cancer, indépendamment de ses fonctions éventuelles dans le noyau. Nous avons démontré par microscopie à force atomique et à l’aide de méthodes biochimiques, que YB-1 se lie aux ARNm d'une manière coopérative à l’ARNm, ce qui a des conséquences directes sur sa capacité à sélectionner des ARNm spécifiques et à moduler la traduction. Au-delà de ces recherches, nous nous sommes appuyés sur notre maitrise de la biologie de YB-1 pour développer une méthode innovante pour mettre en évidence les interactions protéine-protéine dans le contexte cellulaire. Nous avons ainsi confirmé à l’aide de cette méthode la capacité de YB-1 de former des oligomères en présence d'ARNm, et également révélé son interaction potentielle avec Lin28.YB-1 is a member of the cold-shock protein superfamily. It binds to both RNA and DNA. Correlations between high level of YB-1, elevated expression of P-glycoprotein MDR1 and poor patient prognosis were made for several types of cancer. The role of YB-1 in cancerogenesis can be accounted by several mechanisms: i) activation of transcription; ii) participation in DNA repair; iii) regulation of translation. The first two proposals imply a nuclear localization for YB-1, despite the fact that it appears mainly in the cytoplasm under physiological conditions and the mechanisms for its nuclear accumulation remain unclear. In this work we attempted to identify the mechanisms that trigger the nuclear translocation of YB-1. It appeared that this depends on the level of mRNA in the cytoplasm and thus on active transcription, rather than on the presence of nuclear DNA damages. In contrast to its function in the nucleus, the role of YB-1 in the regulation of translation was clearly established. YB-1 may therefore orchestrate a translation bias in order to promote cancer progression independently of its putative functions in the nucleus. Here we demonstrated, using atomic force microscopy and biochemical methods, that YB-1 binds mRNA in a highly cooperative manner and this has direct consequences on mRNA selection and following translational modulation. Beyond this research, we took advantage of our knowledge of the biology of YB-1 to develop a new method to detect protein-protein interactions in cellular context, using YB-1 as model protein. Besides the fact that we confirmed ability of YB-1 to make oligomers in the presence of mRNA, we also highlighted its potential interaction with Lin28, using this method

Inhibition of abasic site cleavage in bubble DNA by multifunctional protein YB-1

International audienceY-box binding protein 1 (YB-1) is widely known to participate in a multiple DNA and RNA processing events in theliving cell. YB-1 is also regarded as a putative component of DNA repair. This possibility is supported by relocalizationof YB-1 into the nucleus following genotoxic stress. Increased affinity of YB-1 for damaged DNA, especially in its singlestrandedform, and its functional interaction with proteins responsible for the initiation of apurinic/apyrimidinic (AP)site repair, namely, AP endonuclease 1 and DNA glycosylase NEIL1, suggest that YB-1 could be involved in the repairof AP sites as a regulatory protein. Here we show that YB-1 has a significant inhibitory effect on the cleavage of AP siteslocated in single-stranded DNA and in DNA bubble structures. Such interference may be considered as a possiblemechanismto prevent single-stranded intermediates of DNA replication, transcription and repair frombeing convertedinto highly genotoxic DNA strand breaks, thus allowing the cell to coordinate different DNA processing mechanisms

Probing protein interactions in living mammalian cells on a microtubule bench

International audienceMicrotubules are μm-long cylinders of about 25 nm in diameter which are present in the cytoplasm of eukaryotic cells. Here, we have developed a new method which uses these cylindrical structures as platforms to detect protein interactions in cells. The principle is simple: a protein of interest used as bait is brought to microtubules by fusing it to Tau, a microtubule-associated protein. The presence of a protein prey on microtubules then reveals an interaction between bait and prey. This method requires only a conventional optical microscope and straightforward fluorescence image analysis for detection and quantification of protein interactions. To test the reliability of this detection scheme, we used it to probe the interactions among three mRNA-binding proteins in both fixed and living cells and compared the results to those obtained by pull-down assays. We also tested whether the molecular interactions of Cx43, a membrane protein, can be investigated with this system. Altogether, the results indicate that microtubules can be used as platforms to detect protein interactions in mammalian cells, which should provide a basis for investigating pathogenic protein interactions involved in human diseases

Ago2-dependent processing allows miR-451 to evade the global microRNA turnover elicited during erythropoiesis

MicroRNAs (miRNAs) are sequentially processed by two RNase III enzymes, Drosha and Dicer. miR-451 is the only known miRNA whose processing bypasses Dicer and instead relies on the slicer activity of Argonaute-2 (Ago2). miR-451 is highly conserved in vertebrates and regulates erythrocyte maturation, where it becomes the most abundant miRNA. However, the basis for the non-canonical biogenesis of miR-451 is unclear. Here, we show that Ago2 is less efficient than Dicer in processing pre-miRNAs, but this deficit is overcome when miR-144 represses Dicer in a negative-feedback loop during erythropoiesis. Loss of miR-144-mediated Dicer repression in zebrafish embryos and human cells leads to increased canonical miRNA production and impaired miR-451 maturation. Overexpression of Ago2 rescues some of the defects of miR-451 processing. Thus, the evolution of Ago2-dependent processing allows miR-451 to circumvent the global repression of canonical miRNAs elicited, in part, by the miR-144 targeting of Dicer during erythropoiesis

Inhibition of Transcription Induces Phosphorylation of YB-1 at Ser102 and Its Accumulation in the Nucleus

International audienceThe Y‐box binding protein 1 (YB‐1) is an RNA/DNA‐binding protein regulating geneexpression in the cytoplasm and the nucleus. Although mostly cytoplasmic, YB‐1 accumulates inthe nucleus under stress conditions. Its nuclear localization is associated with aggressiveness andmultidrug resistance of cancer cells, which makes the understanding of the regulatory mechanismsof YB‐1 subcellular distribution essential. Here, we report that inhibition of RNA polymerase II(RNAPII) activity results in the nuclear accumulation of YB‐1 accompanied by its phosphorylationat Ser102. The inhibition of kinase activity reduces YB‐1 phosphorylation and its accumulation inthe nucleus. The presence of RNA in the nucleus is shown to be required for the nuclear retentionof YB‐1. Thus, the subcellular localization of YB‐1 depends on its post‐translational modifications(PTMs) and intracellular RNA distribution

mRNA and DNA selection via protein multimerization: YB-1 as a case study

International audienceTranslation is tightly regulated in cells for keeping adequate protein levels, this task being notably accomplished by dedicated mRNA-binding proteins recognizing a specific set of mRNAs to repress or facilitate their translation. To select specific mRNAs, mRNA-binding proteins can strongly bind to specific mRNA sequences/structures. However, many mRNA-binding proteins rather display a weak specificity to short and redundant sequences. Here we examined an alternative mechanism by which mRNA-binding proteins could inhibit the translation of specific mRNAs, using YB-1, a major translation regulator, as a case study. Based on a cooperative binding, YB-1 forms stable homo-multimers on some mRNAs while avoiding other mRNAs. Via such inhomogeneous distribution, YB-1 can selectively inhibit translation of mRNAs on which it has formed stable multimers. This novel mechanistic view on mRNA selection may be shared by other proteins considering the elevated occurrence of multimerization among mRNA-binding proteins. Interestingly, we also demonstrate how, by using the same mechanism, YB-1 can form multimers on specific DNA structures, which could provide novel insights into YB-1 nuclear functions in DNA repair and multi-drug resistance