{"title":"[Zebrafish Xenographs in Oncology and Personalized Medicine].","authors":"N A Lunina, D R Safina, S V Kostrov","doi":"10.31857/S0026898424030032, EDN: JDCUGG","DOIUrl":"https://doi.org/10.31857/S0026898424030032, EDN: JDCUGG","url":null,"abstract":"<p><p>The bony fish Danio rerio (zebrafish) has become one of the important vertebrate model organisms in biomedical cancer research and is used, among other things, for the development of anticancer drugs using xenotransplantation approaches. The ex utero development of zebrafish, optically transparent tissues in the first month of growth, and the immature adaptive immune system during this period greatly facilitate the manipulation of embryos. For highly aggressive cancers where patient survival may be expected to be only a few months, a zebrafish xenograft assay may be the only appropriate method as it requires only four to seven days. Thousands of embryos can be implanted with biopsy tissue from a patient to produce zebrafish xenografts and to use them to screen a large number of drugs and compounds automatically to develop an effective treatment regimen for a specific patient. This review examines the advantages and disadvantages of the zebrafish model in oncology research. The main focus is on the use of zebrafish xenografts to study metastasis and to create avatars in personalized medicine.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"363-384"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Recombinant VLP Vaccines Synthesized in Plant Expression Systems: Current Updates and Prospects].","authors":"S M Rozov, E V Deineko","doi":"10.31857/S0026898424030047, EDN: JDBSHP","DOIUrl":"https://doi.org/10.31857/S0026898424030047, EDN: JDBSHP","url":null,"abstract":"<p><p>The development and creation of a new generation vaccines based on recombinant proteins that assemble into virus-like particles (VLPs), as well as recombinant proteins in the form of nanoparticles, are promising directions in modern biotechnology. Due to their large size (20-200 nm) and multiplicity of viral antigenic determinants on the surface, VLPs can stimulate strong humoral and cellular immune responses. The main types of VLPs, as well as the features and disadvantages of the main expression systems used for their biosynthesis, are considered in this review. The main focus was on plant expression systems that ensure the biosynthesis of a target recombinant protein from a DNA matrix integrated into the nuclear or chloroplast genomes of a plant (stable expression) or from a matrix for temporary production of the target product (transient expression). Various approaches for increasing the yield of VLP-forming recombinant proteins, including fusion with a transit peptide that directed the protein into the chloroplast, were discussed. The possibility of accumulation of recombinant proteins expressed in plants and intended for creation of VLP-vaccines in another type of nanoparticle, protein bodies, using specific signal sequences was also considered.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"385-402"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Revision of Functionally Relevant and Widely Expressed Long Non-Coding RNAs].","authors":"D Konina, M Skoblov","doi":"10.31857/S0026898424030137, EDN: JBZHXL","DOIUrl":"https://doi.org/10.31857/S0026898424030137, EDN: JBZHXL","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are involved in many cellular processes while displaying high tissue specificity. In contrast, protein-coding genes, including the category of housekeeping ones, exhibit broad expression patterns. The aim of this study was to highlight the functional importance of widely expressed lncRNAs. We analyzed experimental data from cell-growth screen of lncRNA loci in human cells, which allowed us to identify 18 lncRNA hits. Notably, these lncRNAs were not only widely expressed in most human tissues, but also played functional roles within them. Detail investigation revealed them encompass a variety of molecular functions, from cardiomyocyte damage controlling to macrophage class switching. Interestingly, experimental data highlighted the fact that a significant part of these lncRNAs encoded small but functional polypeptides. A set of lncRNAs, NEAT1, SNHG1, SNHG7, SNHG12, SNHG15, SNHG16, MIR17HG, LINC00680, LINC00263 and LINC00339, that were highly likely to be translated into small polypeptides was identified. Additionally, for EPB41L4A-AS1, CRNDE, SNHG6, LINC00493, and LINC01420, a dual function associated with both the RNA sequences and small proteins they encoded was established.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"493-506"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I Yu Shishkin, G F Shtylev, V E Barsky, S A Lapa, O A Zasedateleva, V E Kuznetsova, V E Shershov, V A Vasiliskov, S A Polyakov, A S Zasedatelev, A V Chudinov
{"title":"[Development of Biological Microchips on an Aluminum Support with Cells Made of Brush Polymers].","authors":"I Yu Shishkin, G F Shtylev, V E Barsky, S A Lapa, O A Zasedateleva, V E Kuznetsova, V E Shershov, V A Vasiliskov, S A Polyakov, A S Zasedatelev, A V Chudinov","doi":"10.31857/S0026898424030114, EDN: JCDIJI","DOIUrl":"https://doi.org/10.31857/S0026898424030114, EDN: JCDIJI","url":null,"abstract":"<p><p>A method has been developed for manufacturing biological microchips on an aluminum substrate with hydrophilic cells from brush copolymers with the formation of a matrix of cells using photolithography. The surface of aluminum substrates was previously coated with a thin, durable, moderately hydrophobic layer of cross-linked polymer to prevent contact with the aluminum surface of the components used in the analysis of nucleic acids. Aluminum biochip substrates have high thermal conductivity and low heat capacity, which is important for the development of methods for multiplex PCR analysis on a chip. Oligonucleotide probes were covalently immobilized in the cells of the biochip. The preservation of the hybridization activity of the immobilized DNA probes was demonstrated in a hybridization analysis with a synthetic DNA target representing a section of the sequence of the seventh exon of the human ABO gene. The methods developed can be used in the development of a technology for parallel multiple rapid microanalysis of nucleic acids \"lab on a chip\" for the detection of human somatic and infectious diseases.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"469-481"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I A Goncharova, A A Zarubin, S A Shipulina, Iu A Koroleva, D S Panfilov, B N Kozlov, M S Nazarenko
{"title":"[DNA Methylation Profiling in Aneurysm and Comorbid Atherosclerosis of the Ascending Aorta].","authors":"I A Goncharova, A A Zarubin, S A Shipulina, Iu A Koroleva, D S Panfilov, B N Kozlov, M S Nazarenko","doi":"10.31857/S0026898424030069, EDN: JCOUUW","DOIUrl":"https://doi.org/10.31857/S0026898424030069, EDN: JCOUUW","url":null,"abstract":"<p><p>Atherosclerosis and aneurysm of the aorta are relatively common pathological conditions that remain asymptomatic for a long period of time and have life-threatening and disabling complications. DNA methylation profiling in several regions (a dilated area, a nondilated area, and an atherosclerotic plaque) of the ascending aorta was carried out in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). Differences in methylation level between dilated and normal aortic tissues were detected for two CpG sites of the NR2F1-AS1 gene (|Δβ| > 0.2 and FDR < 0.05). In total, 586/480 differentially methylated CpG sites (DMSs) were identified by comparing atherosclerotic plaque samples with dilated/normal aortic tissues; 323/234 of the DMSs were hypermethylated and 263/246 were hypomethylated in atherosclerotic plaques. Most DMSs were in introns and intergenic regions; 88.2% of the DMSs were in the binding sites of transcription factors, among which ZNf263, ZFP148, PATZ1, NRF1, TCF12, and EGR1 play a role in the pathogenesis of atherosclerosis of various arteries and ELK1, ETS1, and KLF15 play a role in aortic aneurysms. Sixteen DMSs were found in the regions of the genes CMIP, RPH3AL, XRCC1, GATA5, EXD3, KCNC2, HIVEP3, ADCY9, CDCP2, FOLR1, WT1, MGMT, GAS2, CA1, PRSS16, and ANK3, whose protein products are involved in both aortic dissection and atherosclerosis in various arterial circulation regions. The protein products of the genes are involved in a wide range of biological processes, including mesenchyme development (GO:0060485; FOLR1, WT1, GATA5, HIVEP3, and KCNC2) and positive regulation of DNA metabolic processes (GO:0051054; MGMT, WT1, and XRCC1).</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"414-424"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Participation of Proteins of the CPSF Complex in Polyadenylation of Transcripts Read by RNA Polymerase III from SINEs].","authors":"I G Ustyantsev, O R Borodulina, D A Kramerov","doi":"10.31857/S0026898424030083, EDN: JCHEYP","DOIUrl":"https://doi.org/10.31857/S0026898424030083, EDN: JCHEYP","url":null,"abstract":"<p><p>SINEs are mobile genetic elements of multicellular eukaryotes that arose during evolution from various tRNAs, as well as from 5S rRNA and 7SL RNA. Like the genes of these RNAs, SINEs are transcribed by RNA polymerase III. The transcripts of some mammalian SINEs have the capability of AAUAAA-dependent polyadenylation, which is unique for transcript generated by RNA polymerase III. Despite a certain similarity with canonical polyadenylation of mRNAs (transcripts of RNA polymerase II), these processes apparently differ significantly. The purpose of this work is to evaluate how important for polyadenylation of SINE transcripts are proteins of the CPSF complex formed by mPSF and mCF subcomplexes which direct mRNA polyadenylation. In HeLa cells, siRNA knockdowns of the CPSF components were carried out, after which the cells were transfected with plasmid constructs containing SINEs. A decrease in polyadenylation of the SINE transcripts as a result of the knockdown of the proteins was evaluated by Northern-hybridization. It turned out that the CPSF components, such as Wdr33 and CPSF30, contributed to the polyadenylation of SINE transcriptions, while the knockdown of CPSF100, CPSF73, and symplekin did not reduce the polyadenylation of these transcripts. Wdr33 and CPSF30, along with the CPSF160 and Fip1 previously studied, are components of the subcomplex mPSF responsible for mRNA polyadenylation. Thus, the available data suggest the importance of all mPSF proteins for polyadenylation of SINE transcripts. At the same time, CPSF100, CPSF73, and symplekin, forming the subcomplex mCF, are responsible for the cleavage of pre-mRNA; therefore, their non-participation in the polyadenylation of SINE transcriptions seems quite natural.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"437-447"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Cytoplasmic mRNA Transport: Adaptors of mRNA Binding to Microtubule Motor Proteins].","authors":"Y A Vdovina, S G Georgieva, D V Kopytova","doi":"10.31857/S0026898424030018, EDN: JDPLWQ","DOIUrl":"https://doi.org/10.31857/S0026898424030018, EDN: JDPLWQ","url":null,"abstract":"<p><p>The process of mRNA localization in the cytoplasm involves the directed transport of mRNP particles using the microtubule system. This transport is mediated and regulated by specific factors-adaptors between mRNA molecules and microtubule motor proteins. Adaptors are a key link in the mechanism of mRNA transport, but to date their identity and functioning are mostly unknown. In this review, we examine the features and importance of adaptor proteins in mRNA transport during oogenesis and in neuronal function. This article summarizes recent data on mRNA binding adaptors in the cytoplasm and the mechanisms of their interaction with microtubule motor proteins.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"335-348"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A F Arutyunyan, M S Aksenova, A A Kostyukov, A A Stomakhin, D N Kaluzhny, A L Zhuze
{"title":"[Synthesis of a Bisbenzoxazole Analogue of Hoechst 33258 as a Potential GC-Selective DNA Ligand].","authors":"A F Arutyunyan, M S Aksenova, A A Kostyukov, A A Stomakhin, D N Kaluzhny, A L Zhuze","doi":"10.31857/S0026898424030123, EDN: JCCURC","DOIUrl":"https://doi.org/10.31857/S0026898424030123, EDN: JCCURC","url":null,"abstract":"<p><p>Using a computer modeling approach, we proposed a structure for a potential GC-specific DNA ligand, which could form a complex with DNA in the minor groove similar to that formed by Hoechst 33258 at DNA AT-enriched sites. According to this model, <b>MBoz2A</b>, a bisbenzoxazole ligand, was synthesized. The results of spectrophotometric methods supported the complex formation of the compound under study with DNA differing in the nucleotide composition.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"482-492"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M M Kurshakova, A N Krasnov, E N Nabirochkina, S G Georgieva
{"title":"[Drosophila melanogaster Paip2 Binds ENY2 and Interacts with the TREX-2 Complex in Histone mRNP Particles].","authors":"M M Kurshakova, A N Krasnov, E N Nabirochkina, S G Georgieva","doi":"10.31857/S0026898424030095, EDN: JCFDHO","DOIUrl":"https://doi.org/10.31857/S0026898424030095, EDN: JCFDHO","url":null,"abstract":"<p><p>ENY2 is an evolutionarily conserved multifunctional protein and is a member of several complexes that regulate various stages of gene expression. ENY2 is a subunit of the TREX-2 complex, which is necessary for the export of bulk mRNA from the nucleus to the cytoplasm through the nuclear pores in many eukaryotes. The wide range of ENY2 functions suggests that it can also associate with other protein factors or complexes. In a search for proteins that interact with ENY2 of Drosophila melanogaster, a cDNA library was screened in a yeast two-hybrid system. ENY2 was thus found to interact with the RNA-binding protein Paip2. Paip2 directly bound ENY2 in vitro and interacted with ENY2 in vivo at the molecular and genetic levels. Paip2 was capable of association with the ENY2-containing TREX-2 complex. Paip2 was present at the locus of the histone gene cluster. Both Paip2 and ENY2 were detected at histone locus body (HLBs), nuclear structure where coordinated histone mRNA transcription and processing take place. Paip2 and subunits of the TREX-2 complex were shown to associate with histone mRNP particles. A Paip2 knockdown via RNA interference resulted in decreased binding of TREX-2 subunits to histone mRNPs. Thus, Paip2 was identified as a new partner protein of ENY2 within the TREX-2 complex and suggested to participate in TREX-2 binding to histone mRNPs.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"448-461"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[What Actin and Myosin Do in the Nucleus: New Functions of the Well-Known Proteins].","authors":"A A Saidova, I A Vorobjev","doi":"10.31857/S0026898424030029, EDN: JDMKVN","DOIUrl":"https://doi.org/10.31857/S0026898424030029, EDN: JDMKVN","url":null,"abstract":"<p><p>The functions of actin and its motor proteins myosins in the cytoplasm have been the subject of research for more than 100 years, but the existence and function of these proteins in the nucleus has been a matter of debate until recently. Recent data has clarified the role of actin and myosin molecules in controlling the dynamics of processes in the cell nucleus, chromatin organization and genome integrity. New microscopy techniques and the use of modified actin-binding probes have made it possible for the first time to directly visualize the polymerization of actin filaments in the nucleus of living cells. Here we discuss the processes that control the dynamic balance of actin and myosins between the nucleus and the cytoplasm, as well as the role of these proteins in the regulation of transcription, DNA repair, chromatin reorganization, tumor transformation and cell differentiation.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"349-362"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}