{"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}
{"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}
M L Nikitina, P A Milyaeva, I V Kuzmin, L N Nefedova
{"title":"[Study of the Gut Transcriptomic Response in Drosophila melanogaster with Knockdown of Gagr, Domesticated gag Gene of Errantiviruses].","authors":"M L Nikitina, P A Milyaeva, I V Kuzmin, L N Nefedova","doi":"10.31857/S0026898424030076, EDN: JCKOKP","DOIUrl":"https://doi.org/10.31857/S0026898424030076, EDN: JCKOKP","url":null,"abstract":"<p><p>As a result of molecular domestication of the gag gene of errantiviruses, the Gagr gene was formed in the genome of Drosophila melanogaster. It has previously been shown that the Gagr gene is transcribed at the highest level in gut tissues relative to other tissues, and its transcription is most effectively induced in females in response to ammonium persulfate added to the nutrient medium. In the present work, the gut transcriptome of females with knockdown of the Gagr gene was studied in all tissues under standard conditions and under stress conditions caused by ammonium persulfate. It was revealed that in females with knockdown of the Gagr gene, the genes of antimicrobial peptides controlled by the Toll and Imd signaling pathways are activated in the gut. Induction of a stress response by ammonium persulfate revealed disruption of the JAK/STAT and JNK/MAPK signaling pathways and an almost complete absence of activation of the ER-stress and UPR-stress pathways in flies with the Gagr gene knockdown. The data obtained confirm the important role of the Gagr gene in maintaining homeostasis and the immune response.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"425-436"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873052","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 A Kudryavtseva, A V Vlasov, E V Zinovev, D D Yanovskaya, A A Utkina, S M Rastorguev, I V Manukhov
{"title":"[ArdA Protein Specificity against Type I Restriction-Modification Systems].","authors":"A A Kudryavtseva, A V Vlasov, E V Zinovev, D D Yanovskaya, A A Utkina, S M Rastorguev, I V Manukhov","doi":"10.31857/S0026898424030107, EDN: JCEPFL","DOIUrl":"https://doi.org/10.31857/S0026898424030107, EDN: JCEPFL","url":null,"abstract":"<p><p>The ArdA DNA-mimic antirestriction proteins inhibit type I restriction-modification (RMI) systems by binding instead of DNA to RMI. The ArdA specificity to DNA methylation sites recognized by RMI complexes remains poorly understood; i.e., it is unclear whether a particular DNA site is mimicked by ArdA. The ardA genes were cloned from three Gram-positive bacteria: Agrobacterium tumefaciens, Pseudomonas monteilii, and Xanthomonas sp. Antirestriction activities of their products were tested against three Escherichia coli RMI systems differing in DNA recognition/methylation sites. Although similar structures were predicted for the ArdA proteins, the strong specificity to three RMI systems was observed. The results indicate that specific DNA sites may be imitated by DNA mimic ArdA proteins.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 3","pages":"462-468"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873043","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 V Zhilnikova, O S Troitskaya, D D Novak, V V Atamanov, O A Koval
{"title":"[Uveal Melanoma: Molecular and Genetic Mechanisms of Development and Therapeutic Approaches].","authors":"M V Zhilnikova, O S Troitskaya, D D Novak, V V Atamanov, O A Koval","doi":"10.31857/S0026898424020017, EDN: NQWJSC","DOIUrl":"https://doi.org/10.31857/S0026898424020017, EDN: NQWJSC","url":null,"abstract":"<p><p>Uveal melanoma (UM) is a neuroectodermal tumor that results from malignant transformation of melanocytes in the eye uvea, including the iris, the ciliary body, and the choroid. UM accounts for 5% of all melanoma cases and is extremely aggressive with half of the UM patients developing metastases within the first 1-2 years after tumor development. Molecular mechanisms of UM carcinogenesis are poorly understood, but are known to differ from those of skin melanoma. Activating mutations of the GNAQ and GNA11 genes, which code for the large G protein subunits Gq and G11, respectively, are found in 90% of UM patients. The Gaq/PKC/MAPK signaling pathway is a main signaling cascade that leads to the transformation of melanocytes of the uveal tract, and major regulators of the cascade provide targets for the development of drugs. Metastatic UM (MUM) is most often associated with mutations of BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. A combination of a commercial expression test panel of 15 genes and a mutation panel of 7 genes, supplemented with data on the size of the primary tumor, is highly efficient in predicting the risk of metastasis. The risk of metastasis determines the choice of therapy and the patient follow-up regimen. However, no systemic therapy for MUM has been developed to date. New drugs undergoing clinical trials are mostly targeted drugs designed to inhibit the protein products of mutant genes or immunotherapeutic agents designed to stimulate the immune response against specific antigens. In addition to these approaches, potential therapeutic targets of epigenetic regulation of UM development are considered in the review.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 2","pages":"189-203"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362161","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}
S V Marfina, E A Mikhaleva, N V Akulenko, S S Ryazansky
{"title":"[Method of Inducible Knockdown of Essential Genes in OSC Cell Culture of Drosophila melanogaster].","authors":"S V Marfina, E A Mikhaleva, N V Akulenko, S S Ryazansky","doi":"10.31857/S0026898424020137, EDN: NDBKYZ","DOIUrl":"https://doi.org/10.31857/S0026898424020137, EDN: NDBKYZ","url":null,"abstract":"<p><p>An RNA interference-based method was proposed to achieve an inducible knockdown of genes essential for cell viability. In the method, a genetic cassette in which a copper ion-dependent inducible metallothionein promoter controls expression of a siRNA precursor is inserted into a genomic pre-integrated transgene by CRIPSR/Cas9 technology. The endogenous siRNA source allows the gene knockdown in cell cultures that are refractory to conventional transfection with exogenous siRNA. The efficiency of the method was demonstrated in Drosophila ovarian somatic cell culture (OSC) for two genes that are essential for oogenesis: Cul3, encoding a component of the multiprotein ubiquitin-ligase complex with versatile functions in proteostasis, and cut, encoding a transcription factor regulating differentiation of ovarian follicular cells.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 2","pages":"305-313"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362189","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}
L G Bobyleva, T A Uryupina, N V Penkov, M A Timchenko, A D Ulanova, A G Gabdulkhakov, I M Vikhlyantsev, A G Bobylev
{"title":"[The Structural Features of Skeletal Muscle Titin Aggregates].","authors":"L G Bobyleva, T A Uryupina, N V Penkov, M A Timchenko, A D Ulanova, A G Gabdulkhakov, I M Vikhlyantsev, A G Bobylev","doi":"10.31857/S0026898424020143, EDN: MYWWYU","DOIUrl":"https://doi.org/10.31857/S0026898424020143, EDN: MYWWYU","url":null,"abstract":"<p><p>Titin is a multidomain protein of striated and smooth muscles of vertebrates. The protein consists of repeating immunoglobulin-like (Ig) and fibronectin-like (FnIII) domains, which are β-sandwiches with a predominant β-structure, and also contains disordered regions. In this work, the methods of atomic force microscopy (AFM), X-ray diffraction, and Fourier transform infrared spectroscopy were used to study the morphology and structure of aggregates of rabbit skeletal muscle titin obtained in two different solutions: 0.15 M glycine-KOH, pH 7.0 and 200 mM KCl, 10 mM imidazole, pH 7.0. According to AFM data, skeletal muscle titin formed amorphous aggregates of different morphologies in the above two solutions. Amorphous aggregates of titin formed in a solution containing glycine consisted of much larger particles than aggregates of this protein formed in a solution containing KCl. The \"KCl-aggregates\" according to AFM data had the form of a \"sponge\"-like structure, while amorphous \"glycine-aggregates\" of titin formed \"branching\" structures. Spectrofluorometry revealed the ability of \"glycine-aggregates\" of titin to bind to the dye thioflavin T (TT), and X-ray diffraction revealed the presence of one of the elements of the amyloid cross β-structure, a reflection of ~4.6 Å, in these aggregates. These data indicate that \"glycine-aggregates\" of titin are amyloid or amyloid-like. No similar structural features were found in \"KCl-aggregates\" of titin; they also did not show the ability to bind to thioflavin T, indicating the non-amyloid nature of these titin aggregates. Fourier transform infrared spectroscopy revealed differences in the secondary structure of the two types of titin aggregates. The data we obtained demonstrate the features of structural changes during the formation of intermolecular bonds between molecules of the giant titin protein during its aggregation. The data expand the understanding of the process of amyloid protein aggregation.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 2","pages":"314-324"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362195","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 M Schwartz, K A Tatosyan, D V Stasenko, D A Kramerov
{"title":"[Regulation of Transcription by RNA Polymerase III Promotors in the Norm and Pathology].","authors":"A M Schwartz, K A Tatosyan, D V Stasenko, D A Kramerov","doi":"10.31857/S0026898424020032, EDN: NNFJKS","DOIUrl":"https://doi.org/10.31857/S0026898424020032, EDN: NNFJKS","url":null,"abstract":"<p><p>RNA polymerase III synthesizes a wide range of noncoding RNAs shorter than 400 nucleotides in length. These RNAs are involved in protein synthesis (tRNA, 5S rRNA, and 7SL RNA), maturation, and splicing of different types of RNA (RPR, MRP RNA, and U6 snRNA), regulation of transcription (7SK RNA), replication (Y RNA), and intracellular transport (vault RNA). BC200 and BC1 RNA genes are transcribed by RNA polymerase III in neurons only where these RNAs regulate protein synthesis. Mutations in the regulatory elements of the genes transcribed by RNA polymerase III as well as in transcription factors of this RNA polymerase are associated with the development of a number of diseases, primarily oncological and neurological. In this regard, the mechanisms of regulation of the expression of the genes containing various RNA polymerase III promoters were actively studied. This review describes the structural and functional classification of polymerase III promoters, as well as the factors involved in the regulation of promoters of different types. A number of examples demonstrate the role of the described factors in the pathogenesis of human diseases.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 2","pages":"220-233"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362190","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}
V A Ternovoi, E P Ponomareva, E V Protopopova, N L Tupota, T P Mikryukova, V B Loktev
{"title":"[Changes in the Genome of the Tick-Borne Encephalitis Virus during Cultivation].","authors":"V A Ternovoi, E P Ponomareva, E V Protopopova, N L Tupota, T P Mikryukova, V B Loktev","doi":"10.31857/S0026898424020093, EDN: NILAFS","DOIUrl":"https://doi.org/10.31857/S0026898424020093, EDN: NILAFS","url":null,"abstract":"<p><p>The tick-borne encephalitis virus (TBEV) strain C11-13 (GenBank acc. no. OQ565596) of the Siberian genotype was previously isolated from the brain of a deceased person. TBEV C11-13 variants obtained at passages 3 and 8 in SPEV cells were inoculated into the brains of white mice for subsequent passages. Full genome sequences of all virus variants were analyzed by high-throughput sequencing. A total of 41 single nucleotide substitutions were found to occur mainly in the genes for the nonstructural proteins NS3 and NS5 (GenBank MF043953, OP902894, and OP902895), and 12 amino acid substitutions were identified in the deduced protein sequences. Reverse nucleotide and amino acid substitutions were detected after three passages through mouse brains. The substitutions restored the primary structures that were characteristic of the isolate C11-13 from a human patient and changed during the eight subsequent passages in SPEV cells. In addition, the 3'-untranslated region (3'-UTR) of the viral genome increased by 306 nt. The Y3 and Y2 3'-UTR elements were found to contain imperfect L and R repeats, which were probably associated with inhibition of cellular XRN1 RNase and thus involved in the formation of subgenomic flaviviral RNAs (sfRNAs). All TBEV variants showed high-level reproduction in both cell cultures and mouse brains. The genomic changes that occurred during successive passages of TBEV are most likely due to its significant genetic variability, which ensures its efficient reproduction in various hosts and its broad distribution in various climatic zones.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 2","pages":"282-294"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362186","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}