Acta Naturae最新文献_第2页

Test System for Studying Biotin Transport upon SLC5A6 Gene Inactivation. SLC5A6基因失活时生物素转运研究的测试系统

IF 2 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27645

A Yu Rudenko, P A Zotova, O A Averina, A V Priymak, M P Rubtsova, S S Mariasina, R M Ozhiganov, O A Dontsova, P V Sergiev

{"title":"Test System for Studying Biotin Transport upon SLC5A6 Gene Inactivation.","authors":"A Yu Rudenko, P A Zotova, O A Averina, A V Priymak, M P Rubtsova, S S Mariasina, R M Ozhiganov, O A Dontsova, P V Sergiev","doi":"10.32607/actanaturae.27645","DOIUrl":"10.32607/actanaturae.27645","url":null,"abstract":"This paper introduces a test system for the investigation of biotin transport following inactivation of the SLC5A6 gene, which encodes the sodium-dependent multivitamin transporter SLC5A6. The aim was to develop a method for assessing the efficiency of biotin penetration across the cell membrane following inactivation of the SLC5A6 gene and to explore the feasibility of delivering biotin derivatives into cells independent of SLC5A6. The test system is built upon modified HEK293 cell lines with overexpression of the BirA* biotin ligase, with the first line comprising a functional SLC5A6 gene and the second one involving an inactivated version of this gene mimicking impaired biotin transport. This test system was used to investigate the transport of biotin and its two derivatives, namely the biotin conjugate with p-aminophenylalanine (Bio-1) and biotin methyl ester (Bio-2), through the cell membrane. It has been determined that biotin and its methyl ester (Bio-2) can enter cells independently of the SLC5A6 transporter, which points to the presence of alternative transport pathways. The biotin derivative Bio-1, which contains p-aminophenylalanine, is internalized into cells solely through the hSMVT transporter. The novel test system will serve as a tool for investigating the pathways involved in vitamin entry into cells and for developing therapeutic strategies for individuals with mutations in the SLC5A6 gene, as well as other transport-related genes.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"119-129"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342458","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}

引用次数: 0

p2rx3 Knockout Mice Have Altered Energy Metabolism in Hippocampal Neurons. p2rx3基因敲除小鼠海马神经元能量代谢改变

IF 2 4区生物学

Acta Naturae Pub Date : 2025-07-01 DOI: 10.32607/actanaturae.27551

A S Zelentsova, M V Pokrovskii, E A Patrakhanov, V S Shmigerova, M Yu Skorkina, A V Deykin

{"title":"p2rx3 Knockout Mice Have Altered Energy Metabolism in Hippocampal Neurons.","authors":"A S Zelentsova, M V Pokrovskii, E A Patrakhanov, V S Shmigerova, M Yu Skorkina, A V Deykin","doi":"10.32607/actanaturae.27551","DOIUrl":"10.32607/actanaturae.27551","url":null,"abstract":"The hippocampus is a key component of the brain that is associated with the formation of longterm memory, the energy metabolism of neurons playing a pivotal role in its mechanisms. The P2X3 receptor in the hippocampus is considered an attractive target when searching for novel biologically active substances that could work to reduce anxiety, epileptic conditions, and improve cognitive functions. In this work, the intensity of mitochondrial respiration, the glycolytic capacity, and the energy phenotype of hippocampal neurons were studied in p2rx3 knockout mice. The p2rx3 knockout mice were engineered by genome editing using the CRISPR/Cas9 system. The primary mixed culture of hippocampal neurons was derived from two-day-old newborn mice with the p2rx3-/- and p2rx3+/- genotypes. Mitochondrial respiration was measured on a Seahorse Bioscience HS mini Cell Metabolism Analyzer (Agilent, USA) using the appropriate kits for the Mitostress test, glycotest, and energy phenotype assessment test. The transgenic mice with the p2rx3-/- genotype were characterized by an aerobic type of mitochondrial respiration, an increase in ATP production by 84.4% (p < 0.05), an increase in maximum respiration by 72.3% (p < 0.05), and a 36% (p < 0.05) increase in the respiratory reserve. Meanwhile, the spare respiratory capacity of mitochondria, the rate of glycolysis, and the glycolytic capacity in these mice were reduced by 36.6, 75.7 and 78.6% (p < 0.05), respectively. Our findings indicate that mitochondria work at close to maximum energy capacity. The p2rx3 knockout animals are a unique model for the search for pharmacological targets that can help correct the energy metabolism of brain cells and eliminate cognitive dysfunctions.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 3","pages":"49-55"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342531","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}

引用次数: 0

The Hypomethylating Agent 5-Azacitidine Potentiates the Effect of RAS and Sp1 Inhibitors in Neuroblastoma Cells. 低甲基化剂5-阿扎胞苷增强RAS和Sp1抑制剂在神经母细胞瘤细胞中的作用。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27558

K A Ivanenko, A V Snezhkina, M A Zolotovskaia, P V Spirin, O G Leonova, V I Popenko, A V Kudryavtseva, A A Buzdin, V S Prassolov, T D Lebedev

{"title":"The Hypomethylating Agent 5-Azacitidine Potentiates the Effect of RAS and Sp1 Inhibitors in Neuroblastoma Cells.","authors":"K A Ivanenko, A V Snezhkina, M A Zolotovskaia, P V Spirin, O G Leonova, V I Popenko, A V Kudryavtseva, A A Buzdin, V S Prassolov, T D Lebedev","doi":"10.32607/actanaturae.27558","DOIUrl":"10.32607/actanaturae.27558","url":null,"abstract":"Neuroblastoma is a malignant solid tumor caused by the transformation of neural crest cells. Neuroblastoma predominantly occurs in children and is associated with a poor prognosis. In this regard, the development of novel approaches to neuroblastoma treatment, including combination therapy, is relevant. DNA hypermethylation of neuroblastoma cells indicates that it is possible to use hypomethylating agents in a combination therapy of the disease. In order to identify effective combinations of antitumor drugs, we analyzed the transcriptomic changes that take place in neuroblastoma SH-SY5Y cells after treatment with the hypomethylating agent 5-azacitidine and then experimentally tested the effectiveness of these combinations. Mithramycin A and lonafarnib were the two drugs that, in combination with 5-azacitidine, appeared to exert a synergistic effect on SH-SY5Y cell death. These drugs inhibit the signaling pathway associated with the transcription factor Sp1 and RAS-MAPK signaling pathway, which are activated by 5-azacitidine. An analysis of the signaling pathways also revealed an activation of the signaling pathways associated with neuroblastoma cell differentiation, as well as apoptosis induction, as confirmed by multiplex and confocal microscopy. Hence, by analyzing the changes in the signaling pathways, the mechanisms of cell death and cell adaptation to hypomethylating agents can be understood, and this can be further used to develop novel therapeutic approaches to neuroblastoma therapy.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"86-97"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793148","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}

引用次数: 0

Classification and Quantification of Unproductive Splicing Events. 非生产性剪接事件的分类与量化。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27572

L G Zavileyskiy, E A Chernyavskaya, M A Vlasenok, D D Pervouchine

{"title":"Classification and Quantification of Unproductive Splicing Events.","authors":"L G Zavileyskiy, E A Chernyavskaya, M A Vlasenok, D D Pervouchine","doi":"10.32607/actanaturae.27572","DOIUrl":"10.32607/actanaturae.27572","url":null,"abstract":"In eukaryotic cells, the nonsense-mediated decay (NMD) pathway degrades mRNAs with premature stop codons. The coupling between NMD and alternative splicing (AS) generates NMD-sensitive transcripts (NMD targets, NMDTs) that play an important role in the gene expression regulation via the unproductive splicing mechanism. Understanding this mechanism requires proper identification of NMDT-generating AS events. Here, we developed NMDj, a tool for the identification, classification and quantification of NMDTgenerating AS events which does not rely on the best matching transcript partner principle employed by the existing methods. Instead, NMDj uses a set of characteristic introns that discriminate NMDTs from all protein-coding transcripts. The benchmark on simulated RNA-Seq data demonstrated that NMDj allows to quantify NMDT-generating AS events with better precision compared to other existing methods. NMDj represents a generic method suitable for the accurate classification of arbitrarily complex AS events that generate NMDTs. The NMDj pipeline is available through the repository https://github.com/zavilev/NMDj/.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"75-85"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793206","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}

引用次数: 0

Extracellular Vesicles As a Source of Biomarkers for Cancer Diagnosis. 细胞外囊泡作为癌症诊断的生物标志物来源。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27591

L A Ovchinnikova, Y A Lomakin

引用次数: 0

Monomeric α-Synuclein Real-Time Induced Conversion: A New Approach to the Diagnostics of Neurodegenerative Synucleinopathies with Weak RT-QuIC Responses. 单分子α-突触核蛋白实时诱导转化：一种诊断弱RT-QuIC反应神经退行性突触核蛋白病的新方法。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27530

D A Orlova, A A Kudriaeva, N A Kolotyeva, E O Ivanova, E Yu Fedotova, P P Tregub, A B Salmina, S N Illarioshkin, A A Belogurov Jr

{"title":"Monomeric α-Synuclein Real-Time Induced Conversion: A New Approach to the Diagnostics of Neurodegenerative Synucleinopathies with Weak RT-QuIC Responses.","authors":"D A Orlova, A A Kudriaeva, N A Kolotyeva, E O Ivanova, E Yu Fedotova, P P Tregub, A B Salmina, S N Illarioshkin, A A Belogurov Jr","doi":"10.32607/actanaturae.27530","DOIUrl":"10.32607/actanaturae.27530","url":null,"abstract":"Neurodegenerative disorders classified as synucleinopathies (Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy) are characterized by the accumulation of aberrant α-synuclein aggregates in neurons and glial cells. These diseases manifest clinically several years after the initial formation of pathological protein aggregates in the brain, making early and accurate diagnosis challenging. In recent years, a new method, which is based on real-time quaking-induced conversion (RT-QuIC) of α-synuclein, has been developed and validated. This technology holds great promise as a powerful diagnostic tool for the early and precise identification of synucleinopathies, potentially opening new horizons in the study of neurodegenerative diseases. RT-QuIC detects misfolded α-synuclein aggregates in human physiological fluids by introducing an excess of recombinant α-synuclein, which undergoes conformational conversion in an exponential, prion-like manner. The production of high-quality recombinant α-synuclein is a critical step in the effective application of this method, as protein purity significantly affects the sensitivity and specificity of the assay - key factors in its diagnostic utility. Using a three-step chromatographic purification protocol, we produced recombinant monomeric α-synuclein with a purity exceeding 97% from the periplasmic fraction of bacterial cells. While higher purity increases the assay duration, it also reduces the background signal and permits extended incubation times, which are essential for reliably detecting synucleinopathies with weak RT-QuIC responses, such as the cerebellar subtype of multiple-system atrophy. The data presented support the conclusion that optimized components of the RT-QuIC system will enable an accurate diagnosis of neurodegenerative synucleinopathies.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"110-117"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793144","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}

引用次数: 0

Two Key Substitutions in the Chromophore Environment of mKate2 Produce an Enhanced FusionRed-like Red Fluorescent Protein. mKate2发色团环境中的两个关键替换产生增强的fusionred样红色荧光蛋白。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27545

D A Ruchkin, A S Gavrikov, D V Kolesov, A Yu Gorokhovatsky, T V Chepurnykh, A S Mishin, E G Maksimov, N V Pletneva, V Z Pletnev, A M Pavlova, V A Nikitin, A M Bogdanov

{"title":"Two Key Substitutions in the Chromophore Environment of mKate2 Produce an Enhanced FusionRed-like Red Fluorescent Protein.","authors":"D A Ruchkin, A S Gavrikov, D V Kolesov, A Yu Gorokhovatsky, T V Chepurnykh, A S Mishin, E G Maksimov, N V Pletneva, V Z Pletnev, A M Pavlova, V A Nikitin, A M Bogdanov","doi":"10.32607/actanaturae.27545","DOIUrl":"10.32607/actanaturae.27545","url":null,"abstract":"Red fluorescent proteins (RFPs) are often probes of choice for living tissue microscopy and whole-body imaging. When choosing a specific RFP variant, the priority may be given to the fluorescence brightness, maturation rate, monomericity, excitation/emission wavelengths, and low toxicity, which are rarely combined in an optimal way in a single protein. If additional requirements such as prolonged fluorescence lifetime and/or blinking ability are applied, the available repertoire of probes could dramatically narrow. Since the entire diversity of conventional single-component RFPs belongs to just a few phylogenetic lines (DsRed-, eqFP578- and eqFP611-derived being the major ones), it is not unexpected that their advantageous properties are split between close homologs. In such cases, a systematic mutagenetic analysis focusing on variant-specific amino acid residues can shed light on the origins of the distinctness between related RFPs and may aid in consolidating their strengths in new RFP variants. For instance, the protein FusionRed, despite being efficient in fluorescence labeling thanks to its good monomericity and low cytotoxicity, has undergone considerable loss in fluorescence brightness/lifetime compared to the parental mKate2. In this contribution, we describe a fast-maturing monomeric RFP designed semi-rationally based on the mKate2 and FusionRed templates that outperforms both its parents in terms of molecular brightness, has extended fluorescence lifetime, and displays a spontaneous blinking pattern that is promising for nanoscopy use.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"110-117"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793149","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}

引用次数: 0

Cis-regulatory Function of the Pou5f1 Gene Promoter in the Mouse MHC Locus. Pou5f1基因启动子在小鼠MHC位点的顺式调控功能。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27596

V V Ermakova, E V Aleksandrova, A A Kuzmin, A N Tomilin

{"title":"Cis-regulatory Function of the Pou5f1 Gene Promoter in the Mouse MHC Locus.","authors":"V V Ermakova, E V Aleksandrova, A A Kuzmin, A N Tomilin","doi":"10.32607/actanaturae.27596","DOIUrl":"10.32607/actanaturae.27596","url":null,"abstract":"The Pou5f1 gene encodes the Oct4 protein, one of the key transcription factors required for maintaining the pluripotent state of epiblast cells and the viability of germ cells. However, functional genetics provides convincing evidence that Pou5f1 has a broader range of functions in mouse ontogeny, including suppression of atherosclerotic processes. Related studies have primarily focused on the functions of the Oct4 protein, while the regulatory sequences within the Pou5f1 gene have not been considered. In this study, we have developed a genetic model which is based on mouse embryonic stem cells (ESCs) for assessing the roles of the Pou5f1 gene promoter in the transcriptional regulation of neighboring genes within the major histocompatibility complex (MHC) locus. We have demonstrated that deletion of this promoter affects the expression of selected genes within this locus neither in ESCs nor in the trophoblast derivatives of these cells. A notable exception is the Tcf19 gene, which is upregulated upon Pou5f1 promoter deletion and might be associated with the atherosclerosis pathology due to its pro-inflammatory activity. The developed genetic model will pave the way for future studies into the functional contribution of the cis-regulatory association of Pou5f1, Tcf19, and, possibly, other genes with the atherosclerotic phenotype previously reported for mice carrying the Pou5f1 promoter deletion in vascular endothelial and smooth muscle cells.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"64-74"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793205","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}

引用次数: 0

The Emergence of a Novel Insertional Mutation in the BCR::ABL/p210 Oncogene in B-Cell Acute Lymphoblastic Leukemia (B-ALL) Correlates with the Development of Resistance to Several Tyrosine Kinase Inhibitors. b细胞急性淋巴细胞白血病（B-ALL）中BCR::ABL/p210癌基因新插入突变的出现与几种酪氨酸激酶抑制剂耐药性的发展相关。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27539

K V Bogdanov, E S Kudryavtseva, Y N Lobacheva, O V Merzlikina, Y V Mirolyubova, R A Vlasik, R Sh Badaev, E G Lomaia

{"title":"The Emergence of a Novel Insertional Mutation in the BCR::ABL/p210 Oncogene in B-Cell Acute Lymphoblastic Leukemia (B-ALL) Correlates with the Development of Resistance to Several Tyrosine Kinase Inhibitors.","authors":"K V Bogdanov, E S Kudryavtseva, Y N Lobacheva, O V Merzlikina, Y V Mirolyubova, R A Vlasik, R Sh Badaev, E G Lomaia","doi":"10.32607/actanaturae.27539","DOIUrl":"10.32607/actanaturae.27539","url":null,"abstract":"A patient with an immunophenotype characteristic of B-cell acute lymphoblastic leukemia (B-ALL) was found to carry the chromosomal translocation t(9;22)(q34;q11), or Philadelphia (Ph) chromosome and less common variant of the chimeric oncogene BCR::ABL/p210. No additional mutations in the BCR::ABL gene, including point mutations, insertions, or deletions, were identified in the disease onset characterized by elevated blast cell (77.6%) and leukocyte (48×109/L) counts. Ph+ALL-2012m chemotherapy with imatinib (600 mg) and two consolidation phases resulted in complete hematologic remission and a profound molecular response. However, six months later, the patient had relapsed (blasts: 15%, BCR::ABL/p210: 105%). Three weeks after the initiation of dasatinib therapy (100 mg), the number of blasts had decreased to 4.8%, while the expression level of BCR::ABL/p210 had dropped to 11.8%. Sanger sequencing identified two mutations in the BCR::ABL oncogene; namely, the point mutation F317L and a new insertion of nine nucleotides previously not detected. In the latter case, the amino acid lysine at position 294 was replaced by four new amino acid residues: K294SPSQ. Therapy with bosutinib and inotuzumab led to the disappearance of one leukemia clone with the F317L mutation, but the presence of another clone carrying a nine-nucleotide insertion was observed. The switch to ponatinib+blinatumomab chemotherapy was effective, resulting in the disappearance of the insertion. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an available HLA-matched unrelated donor resulted in complete clinical and hematologic remission, including a complete molecular response. Six months after allo-HSCT, minimal residual disease monitoring showed maintenance of complete remission.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"52-57"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793147","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}

引用次数: 0

Integration of HiMoRNA and RNAChrom: Validation of the Functional Role of Long Non-coding RNAs in the Epigenetic Regulation of Human Genes Using RNA-Chromatin Interactome Data. HiMoRNA和RNAChrom的整合：利用rna -染色质相互作用组数据验证长链非编码rna在人类基因表观遗传调控中的功能作用。

IF 2 4区生物学

Acta Naturae Pub Date : 2025-04-01 DOI: 10.32607/actanaturae.27543

I S Ilnitskiy, G K Ryabykh, D A Marakulina, A A Mironov, Yu A Medvedeva

{"title":"Integration of HiMoRNA and RNAChrom: Validation of the Functional Role of Long Non-coding RNAs in the Epigenetic Regulation of Human Genes Using RNA-Chromatin Interactome Data.","authors":"I S Ilnitskiy, G K Ryabykh, D A Marakulina, A A Mironov, Yu A Medvedeva","doi":"10.32607/actanaturae.27543","DOIUrl":"10.32607/actanaturae.27543","url":null,"abstract":"Long non-coding RNAs (lncRNAs) play a crucial role in the epigenetic regulation of gene expression by recruiting chromatin-modifying proteins to specific genomic loci. Two databases, previously developed by our groups, HiMoRNA and RNA-Chrom, provide valuable insights into this process. The former contains data on epigenetic modification regions (peaks) correlated with lncRNA expression, while the latter offers genome-wide RNA-chromatin interaction data for tens of thousands of RNAs. This study integrated the two resources to generate experimentally supported, interpretable hypotheses regarding lncRNA-mediated epigenetic gene expression regulation. We adapted the web interfaces of HiMoRNA and RNA-Chrom to enable the retrieval of chromatin contacts for each \"lncRNA-pigenetic modification-ssociated gene\" triad from HiMoRNA, either at specific genomic loci or genome-wide via RNA-Chrom. The integration analysis revealed that for the lncRNAs MALAT1, HOXC-AS2, NEAT1, NR2F1-AS1, PVT1, and MEG3, most HiMoRNA peaks are located within 25 kb of their RNA-Chrom contacts. Further investigation confirmed the RNA-hromatin contacts of MIR31HG and PVT1 lncRNAs, with HiMoRNA peaks for H3K27ac and H3K27me3 marks in the loci of the genes GLI2 and LATS2, respectively, which are known to be regulated by these RNAs. Thus, the integration of HiMoRNA and RNA-Chrom offers a powerful platform to elucidate the role of specific lncRNAs in the regulation of histone modifications at both individual loci and genome-wide levels. We expect this integration to help significantly advance the functional annotation of human lncRNAs.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"98-109"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793143","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}

引用次数: 0