M. M. Kurshakova, Y. A. Yakusheva, S. G. Georgieva
{"title":"TREX-2 mRNA Export Complex Interacts with HLB Component FLASH and Is Recruited to Processed Histone mRNAs","authors":"M. M. Kurshakova, Y. A. Yakusheva, S. G. Georgieva","doi":"10.1134/S1607672925601167","DOIUrl":"10.1134/S1607672925601167","url":null,"abstract":"<p>Disruption of the normal expression of histone genes lead to the development of various pathologies. One of the key stages of gene expression is the export of mRNA from the nucleus to the cytoplasm. The TREX-2 protein complex regulates the export of the majority of poly(A)-containing mRNAs. Previously, we demonstrated that TREX-2 is also associated with histone mRNP particles and participates in the nuclear export of histone mRNAs, which lack poly(A)-tails. In this study we investigated the interaction of TREX-2 proteins with the histone mRNA processing machinery. It was shown that TREX-2 interacts with the FLASH protein, a key protein of the specialized histone mRNA processing machinery and a component of the histone locus body (HLB). The TREX-2 complex is recruited through its interaction with FLASH to processed histone mRNAs.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"524 1","pages":"503 - 508"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Syngenic Mouse Model of Breast Cancer Expressing Human ERBB2 and NanoLuc Luciferase Genes","authors":"E. I. Shramova, S. M. Deyev, G. M. Proshkina","doi":"10.1134/S1607672925601155","DOIUrl":"10.1134/S1607672925601155","url":null,"abstract":"<p>Syngeneic models are widely used in experimental oncology both for modeling tumor diseases and for testing anticancer drugs. However, when testing targeted drugs aimed at human tumor-associated antigens, the presence of target antigens in the animal’s body is important. In this study, a syngeneic cell line with stable expression of two genes—the <i>ERBB</i>2 gene encoding human epidermal growth factor receptor type 2 (<i>HER</i>2) and the <i>NanoLuc</i> luciferase gene—was created based on murine mammary gland carcinoma. Optical bioimaging methods have proven that the created cell line is characterized by stable expression of <i>ERBB</i>2 and <i>NanoLuc</i> in vitro and in vivo, retains the aggressive growth of the original 4T1 cell line in animals, and forms spontaneous metastases that are detected in the animal’s body by intravital biovisualization methods.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"524 1","pages":"498 - 502"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Two RNA-Binding Regions of PCID2, a Subunit of the TREX-2 mRNA Nuclear Export Complex, Competitively Interact with the 3' Noncoding Region of ras2 mRNA","authors":"Y. A. Vdovina, S. G. Georgieva, D. V. Kopytova","doi":"10.1134/S1607672925600563","DOIUrl":"10.1134/S1607672925600563","url":null,"abstract":"<p>PCID2 protein is a subunit of the eukaryotic complex TREX-2, which is responsible for nuclear export of mRNA. PCID2 plays an important role in the complex, being responsible for the recognition and binding of the mRNA molecule. PCID2 of <i>D. melanogaster</i> interacts with a region of <i>ras</i>2 (fr4_2) mRNA and has two interaction sites located in its PCI domain: the M-PCID2 region, which non-specifically binds to mRNA, and the C-terminal part (C-PCID2), which specifically recognizes the <i>ras</i>2 fr4_2 mRNA sequence. At the same time, specific binding to C-PCID2 requires a preliminary nonspecific interaction with M-PCID2. It remains unclear how the transition from primary nonspecific interaction to specific interaction occurs: whether both regions interact with RNA simultaneously or whether the nonspecific interaction is required only at the first step for subsequent specific binding. This study showed that the binding of M-PCID2 and C-PCID2 to <i>ras</i>2 fr4_2 RNA is competitive. M-PCID2 binds more efficiently and displaces C-PCID2 from the complex with the <i>ras</i>2 mRNA fragment. Thus, additional factors are required to replace the M-PCID2 contact by C-PCID2 during the interaction of the full-length PCID2 protein with <i>ras</i>2 mRNA. We also showed that point mutations in M-PCID2 that disrupt the interaction of the full-length PCID2 with RNA result in a greater association of M-PCID2 with RNA. It is likely that the increased affinity of M-PCID2 for RNA disrupts the ability to replace M-PCID2 with C-PCID2 within the full-length PCID2.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"439 - 443"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Systemic Rearrangement of the Heart Rhythm in the Process of Organism Aging: Spectral Analysis","authors":"A. A. Grinevich, N. K. Chemeris","doi":"10.1134/S1607672925600393","DOIUrl":"10.1134/S1607672925600393","url":null,"abstract":"<p>Changes in the cardiovascular system are systemic during aging. The aim of this work is to describe systemic patterns of changes in heart rate variability (HRV) parameters during aging in healthy subjects. HRV data of 73 healthy subjects aged 11–76 years from the PhysioNet database were used, which were divided into three groups: young (11–17 years old), middle-aged (24–55 years old), and elderly (56–76 years old). Using the Hilbert–Huang method and wavelet analysis, spectral curves of empirical HRV modes were obtained, for which the maxima and their corresponding frequencies were determined. Nine modes were identified. A twofold decrease in the autonomic control modes and, to a lesser extent, in the very-low-frequency modes (0.002–0.04 Hz) was found in the elderly compared to the young. Very-low-frequency HRV oscillations (<0.001 Hz) did not change with age. The results obtained may serve as a basis for physiological interpretation of HRV regulation processes and may be useful in the development of controlled anti-aging therapy.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"486 - 490"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interdomain Interactions of the PCID2 Protein, One of the Subunits of the TREX-2 mRNA Export Complex in Drosophila melanogaster","authors":"Y. A. Vdovina, S. G. Georgieva, D. V. Kopytova","doi":"10.1134/S1607672925600575","DOIUrl":"10.1134/S1607672925600575","url":null,"abstract":"<p>The TREX-2 complex is responsible for the export of mRNA from the nucleus to the cytoplasm and consists of four proteins. It was recently shown that the PCID2 subunit of TREX-2 is responsible for the specific recognition of mRNA by the TREX-2 complex. The majority of the protein contains the PCI domain, which has surfaces for RNA binding. The PCI domain includes the central region of the protein, which has a surface for non-specific RNA binding, M-PCID2, and the C-terminal part of the PCI domain and the C-terminal part of the protein, C-PCID2, which has a surface for specific RNA recognition. The N-terminal part of PCID2 contains a region whose function is unknown. Since the TREX-2 complex binds to only a specific mRNA and only at a specific stage, we hypothesized that the N-terminal part of PCID2 might modulate the binding of C-PCID2 to RNA by binding to it and covering its RNA-binding domain. We showed that the N-terminal region interacts with C-PCID2. The binding of C-PCID2 to RNA in this case is not impaired. In addition, the binding of C-PCID2 to RNA does not disrupt its interaction with the N-terminal part of the protein (N-PCID2). Thus, C-PCID2 can interact with N-PCID2 and RNA by different surfaces. This intrinsic interaction is probably necessary at one of the stages of functioning of the TREX-2 complex.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"458 - 461"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. A. Zolin, A. A. Grigel, S. G. Georgieva, A. N. Krasnov, J. V. Nikolenko
{"title":"MLE/DHX9 Helicase Activity Is Required to Regulate the Expression of a Number of Tissue-Specific Genes on Chromosome 4 in Drosophila melanogaster","authors":"I. A. Zolin, A. A. Grigel, S. G. Georgieva, A. N. Krasnov, J. V. Nikolenko","doi":"10.1134/S1607672925601222","DOIUrl":"10.1134/S1607672925601222","url":null,"abstract":"<p>DHX9 helicase and its ortholog MLE in <i>D. melanogaster</i> participate in different stages of gene expression. Both helicases are important for the formation and functioning of the nervous system in humans and <i>D. melanogaster</i>, respectively. However, the role of helicase activity of DHX9 and MLE in the regulation of gene expression has been poorly studied, and the existing data are quite contradictory. This work is devoted to the study of the role of helicase activity of MLE in the regulation of gene expression in <i>D. melanogaster</i>. A site of intense MLE binding was found on chromosome 4 of <i>D. melanogaster</i>, in locus 102F. It was shown that MLE is a co-activator of expression of the <i>Dyrk3</i>, <i>Toy</i>, <i>Sox102F</i>, <i>Shaven</i>, and <i>Fuss</i> genes located in this locus. For this, the helicase activity of MLE is required. Genes whose expression depends on MLE are expressed at a high level in the nervous system of <i>D. melanogaster</i> and are essential for its proper development. The obtained data contributes to the study of potentially evolutionarily conserved functions of MLE.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"524 1","pages":"509 - 513"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. S. Alexeev, M. A. Konkina, N. N. Kurochkin, M. S. Drenichev
{"title":"Preparation of 6-Azido-2-Chloropurine-2′-Deoxyriboside by Enzymatic Transglycosylation Reaction Catalyzed by Lactobacillus leichmannii Type II Nucleoside Deoxyribosyltransferase","authors":"C. S. Alexeev, M. A. Konkina, N. N. Kurochkin, M. S. Drenichev","doi":"10.1134/S160767292560040X","DOIUrl":"10.1134/S160767292560040X","url":null,"abstract":"<p>6-azido-2-chloropurine-2′-deoxyriboside, a valuable precursor for the preparation of modified 2-chloropurine nucleosides substituted at the 6-position of the heterocyclic base, was obtained by enzymatic transglycosylation. 6-azido-2-chloropurine-2′-deoxyriboside can also be used as a photocross-linking agent to study the nucleic acids—proteins interactions. A type II nucleoside deoxyribosyltransferase from <i>Lactobacillus leichmannii</i> was used as a biocatalyst. The optimal conditions for the formation of 6-azido-2-chloropurine-2′-deoxyriboside using 7-methyl-2′-deoxyguanosine as a carbohydrate residue donor were determined.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"444 - 451"},"PeriodicalIF":0.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of a Comparative Analysis of Different Annotations of the Oryza sativa Rice Genome for In Silico Verification of Predicted Promoter Sequences","authors":"A. N. Bubnova, I. V. Yakovleva, A. M. Kamionskaya","doi":"10.1134/S1607672925600332","DOIUrl":"10.1134/S1607672925600332","url":null,"abstract":"<p>In this study, promoter sequences predicted by the MAHDS method in the <i>Oryza sativa</i> genome were analyzed using three genome annotations: RefSeq NCBI, Rice Genome Annotation Project, and Ensembl. Part of the predicted promoters was found to be located near annotated genes, which indicates their potential functional role. The remaining sequences, considered as potentially novel regulatory elements, were examined using YAPP for the presence of core promoter motifs and their functional combinations. All analyzed predicted promoters contain either an Inr or a TATA motif—the key elements involved in transcription initiation. The identified motif combinations suggest a high likelihood of transcriptional activity in these sequences, and the consistency of the results with annotated data and CAGE-seq signals supports the reliability and applicability of the MAHDS method.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"462 - 465"},"PeriodicalIF":0.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. A. Shamonova, M. S. Koriagina, V. L. Shliapina, O. A. Dontsova, M. P. Rubtsova
{"title":"Protein Complementation Approach for Quantitative and Qualitative Analysis of hTERP in Cell","authors":"M. A. Shamonova, M. S. Koriagina, V. L. Shliapina, O. A. Dontsova, M. P. Rubtsova","doi":"10.1134/S1607672925600514","DOIUrl":"10.1134/S1607672925600514","url":null,"abstract":"<p>The functioning of proteins in a cell cannot be studied without analyzing their content in the cell. The most commonly used method of analysis, Western blotting, cannot always be used due to the impossibility of obtaining antibodies that specifically recognize the protein of interest. At the same time, Western blotting is a semi-quantitative method of analysis and does not allow determining the exact content of protein in the cell. In this work, we used the protein complementation method for the qualitative and quantitative assessment of the hTERP protein content in the cell. Using genome editing, a HiBiT epitope was introduced to the C-terminus of the hTERP protein, the complementation of which with LgBiT restores active luciferase. As a result, we determined the hTERP protein content in the HEK293T cell line.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"452 - 457"},"PeriodicalIF":0.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Jin, Jue-jue Wang, Yan-fei Feng, Bing Chen, Zhao-hua Hu
{"title":"HDAC3 Regulates Ferroptosis via Nrf2–GPX4 Signaling in Colorectal Cancer Cells","authors":"Wei Jin, Jue-jue Wang, Yan-fei Feng, Bing Chen, Zhao-hua Hu","doi":"10.1134/S1607672925600496","DOIUrl":"10.1134/S1607672925600496","url":null,"abstract":"<p>Ferroptosis, an iron-dependent form of regulated cell death, represents an emerging therapeutic vulnerability in colorectal cancer (CRC). However, the epigenetic mechanisms controlling ferroptosis sensitivity in CRC remain poorly understood. Here, we identify histone deacetylase 3 (HDAC3) as a pivotal epigenetic suppressor of ferroptosis. Both pharmacological inhibition and genetic knockdown of HDAC3 significantly enhanced ferroptosis sensitivity, as evidenced by elevated intracellular ferrous iron (Fe<sup>2+</sup>) and lipid peroxidation. Mechanistically, inhibition of HDAC3 reduced the expression of nuclear factor erythroid 2–related factor 2 (NRF2), a master antioxidant transcription factor, thereby leading to downregulation of glutathione peroxidase 4 (GPX4), a central ferroptosis defense gene. Notably, NRF2 knockdown abolished GPX4 downregulation by HDAC3 inhibition, whereas GPX4 overexpression rescued the ferroptotic phenotype caused by HDAC3 depletion. Collectively, these findings define an HDAC3–NRF2–GPX4 axis that suppresses ferroptosis in CRC, and highlight HDAC3 as a potential therapeutic target for ferroptosis-based cancer treatment.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"523 1","pages":"424 - 433"},"PeriodicalIF":0.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1607672925600496.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}