{"title":"Protein-protein interactions as determinants of operon architecture","authors":"Silky Bedi, S.M. Rose, Simerpreet Kaur , Preeti Negi , Sharmistha Sinha","doi":"10.1016/j.bbagen.2025.130794","DOIUrl":"10.1016/j.bbagen.2025.130794","url":null,"abstract":"<div><div>Operons, clusters of genes under a single promoter, often exhibit a specific gene order influencing their physiological function. While functional relatedness is a known factor for clustering, the underlying drivers of gene ordering remain unclear. To investigate this, we analyzed the <em>pdu</em> operon, encoding proteins for 1,2 Pdu bacterial microcompartment. Our bioinformatics revealed no link between the sequence similarity and proximity of the genes in the operon. However quantitative mapping of protein-protein interactions within the operon using a barrage of spectroscopic tools showed a strong correlation between interaction strength and gene proximity. Our data thus indicates that protein-protein interactions play a significant role in determining gene order within the <em>pdu</em> operon, potentially contributing to the efficient assembly and function of these microcompartments.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130794"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shilian Pang , Yurao Chen , Zemao Zheng , Luoshai Wang , Ronghuai Chen , Ming He , Xiang Zhao , Juan Yao , Liyan Jin
{"title":"STAT3-orchestrated gene expression signatures and tumor microenvironment in esophageal squamous cell carcinoma uncovered by single-cell sequencing","authors":"Shilian Pang , Yurao Chen , Zemao Zheng , Luoshai Wang , Ronghuai Chen , Ming He , Xiang Zhao , Juan Yao , Liyan Jin","doi":"10.1016/j.bbagen.2025.130791","DOIUrl":"10.1016/j.bbagen.2025.130791","url":null,"abstract":"<div><h3>Background</h3><div>The progression of Esophageal Squamous Cell Carcinoma (ESCC) can be dissected with greater precision using multi-omics and single-cell RNA sequencing (scRNA-seq) compared to traditional methodologies. These advanced approaches enable a comprehensive understanding of cellular heterogeneity and molecular dynamics, offering higher resolution insights into cancer development. Moreover, analyzing transcription factor regulatory networks provides innovative avenues for identifying cancer biomarkers and therapeutic targets, driving new perspectives in cancer research.</div></div><div><h3>Objective</h3><div>To explore the molecular mechanisms and cellular dynamics of ESCC.</div></div><div><h3>Methods</h3><div>Utilizing bulk-RNA-seq and single-cell transcriptomics, our study identify major cell types, transcriptomic gene and function changes during ESCC progression. Validation experiments in clinical sample tissues and ESCC cell lines to confirm core regulation factor in ESCC.</div></div><div><h3>Results</h3><div>We identified six major cell types in the ESCC scRNA-seq dataset and revealed profound shifts in cellular composition and transcriptional profiles. Notably, STAT3 was found to be a core regulator in ESCC and negatively regulated LHPP expression at promoter sites. Elevated STAT3 and reduced LHPP expression were consistently observed in patient samples, highlighting their inverse relationship in ESCC pathogenesis.</div></div><div><h3>Conclusion</h3><div>This study integrates bulk-seq and scRNA-seq data to reveal the pivotal role of STAT3 in ESCC. STAT3 negatively regulates LHPP expression, driving tumor progression. These findings underscore the therapeutic potential of targeting STAT3 in ESCC. <strong>Key words:</strong> ESCC, single-cell transcriptomics, ESCC microenvironment, STAT3.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130791"},"PeriodicalIF":2.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Compartmentation of multiple metabolic enzymes and their preparation in vitro and in cellulo","authors":"Sayoko Ito-Harashima, Natsuko Miura","doi":"10.1016/j.bbagen.2025.130787","DOIUrl":"10.1016/j.bbagen.2025.130787","url":null,"abstract":"<div><div>Compartmentalization of multiple enzymes <em>in cellulo</em> and <em>in vitro</em> is a means of controlling the cascade reaction of metabolic enzymes. The compartmentation of enzymes through liquid–liquid phase separation may facilitate the reversible control of biocatalytic cascade reactions, thereby reducing the transcriptional and translational burden. This has attracted attention as a potential application in bioproduction. Recent research has demonstrated the existence and regulatory mechanisms of various enzyme compartments within cells. Mounting evidence suggests that enzyme compartmentation allows <em>in vitro</em> and <em>in vivo</em> regulation of cellular metabolism. However, the comprehensive regulatory mechanisms of enzyme condensates in cells and ideal organization of cellular systems remain unknown. This review provides an overview of the recent progress in multiple enzyme compartmentation in cells and summarizes strategies to reconstruct multiple enzyme assemblies <em>in vitro</em> and <em>in cellulo</em>. By examining parallel examples, we have evaluated the consensus and future perspectives of enzyme condensation.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130787"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genome-wide identification and expression analysis of glutamate receptor-like genes in three Dendrobium species","authors":"Miao Zhu, Xuying Wang, Xinran Li","doi":"10.1016/j.bbagen.2025.130789","DOIUrl":"10.1016/j.bbagen.2025.130789","url":null,"abstract":"<div><div>Glutamate receptor-like (<em>GLRs</em>) genes play essential roles in plant growth and development, and in coping with environmental stresses; however, information on <em>GLR</em> genes in <em>Dendrobium</em> species is lacking. We identified 25 <em>GLR</em> genes in three <em>Dendrobium</em> species, which were classified into three subfamilies based on their phylogenetic relationships. These genes have been relatively conserved during evolution. Analysis of cis-acting elements and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations revealed the complexity and diversity of <em>GLR</em> gene regulation and functions. Further, gene expression analysis showed that different <em>GLR</em> members exhibited different expression patterns during <em>Dendrobium</em> growth and development, and some were involved in pathogen infection and in response to hormones. These results provide important information on the <em>GLR</em> gene family of <em>Dendrobium,</em> and a foundation for further functional, and trait regulation and improvement studies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130789"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional involvement of RNAs and intrinsically disordered proteins in the assembly of heterochromatin","authors":"Chikashi Obuse , Jun-ichi Nakayama","doi":"10.1016/j.bbagen.2025.130790","DOIUrl":"10.1016/j.bbagen.2025.130790","url":null,"abstract":"<div><div>Heterochromatin is a highly condensed chromatin structure observed in the nuclei of eukaryotic cells. It plays a pivotal role in repressing undesired gene expression and establishing functional chromosomal domains, including centromeres and telomeres. Heterochromatin is characterized by specific histone modifications and the formation of higher-order chromatin structures mediated by proteins, such as HP1 and Polycomb repressive complexes (PRCs), which recognize the specific histone modifications. Recent studies have identified the involvement of non-coding RNAs (ncRNAs) and intrinsically disordered proteins (IDPs) in heterochromatin, leading to the proposal of a new model in which liquid-liquid phase separation (LLPS) contributes to heterochromatin formation and function. This emerging model not only broadens our understanding of heterochromatin's molecular mechanisms but also provides insights into its dynamic regulation depending on cellular context. Such advancements pave the way for exploring heterochromatin's role in genome organization and stability, as well as its implications in development and disease.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130790"},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantifying redox signalling regulatory transcriptional dynamics in Nardostachys jatamansi under abiotic stress response","authors":"Shubham Joshi , Rohit Joshi","doi":"10.1016/j.bbagen.2025.130788","DOIUrl":"10.1016/j.bbagen.2025.130788","url":null,"abstract":"<div><div>Understanding the responses of Himalayan medicinal plants to multifactorial stresses is crucial in the face of increasing environmental challenges, primarily characterised by frequent temperature and water availability fluctuations. The present study investigates the physiological, biochemical, and transcript variations in the critically endangered Himalayan medicinal plant <em>Nardostachys jatamansi</em> subjected to cold (15 °C and 10 °C for 30 days), drought (6 % PEG for 30 days), and heat stress (30 °C for 24 h). The primary impact of stress was observed through reduced plant biomass and chlorophyll fluorescence. The effects of abiotic stresses were also evident in the modulation of electrolyte leakage, MDA content and H<sub>2</sub>O<sub>2</sub> accumulation. Accumulation of reactive oxygen species was confirmed through DAB and NBT staining, alongside increased DPPH and ABTS radical scavenging activity. Differential expression profiling of the RBOH family transcripts further substantiated the production of ROS. Enhanced enzymatic and non-enzymatic activities were observed under each abiotic stress condition. Additionally, genes specific to the regulatory mevalonate (MVA) pathway (<em>TPS9</em>; <em>HMGR</em>) and the methylerythritol phosphate (MEP) pathway (<em>DXS1</em>; <em>DXR</em>) were found to be differentially regulated. Moreover, differential expression profiling of abiotic stress signalling regulatory transcripts <em>CRLK1</em>, <em>CRLK2</em>, <em>CaM6</em> and <em>ICE1</em> was also discovered. These findings provide valuable insights into the physiological and biochemical profiling of <em>N. jatamansi</em> in response to extreme environmental conditions, significantly aiding our understanding of the adaptation strategies of alpine vegetation for their conservation.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130788"},"PeriodicalIF":2.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andy Y.W. Lam , Yukihide Tomari , Kotaro Tsuboyama
{"title":"No structure, no problem: Protein stabilization by Hero proteins and other chaperone-like IDPs","authors":"Andy Y.W. Lam , Yukihide Tomari , Kotaro Tsuboyama","doi":"10.1016/j.bbagen.2025.130786","DOIUrl":"10.1016/j.bbagen.2025.130786","url":null,"abstract":"<div><div>In order for a protein to function, it must fold into its proper three-dimensional structure. Otherwise, improperly folded proteins are typically prone to aggregate through a process that is detrimental to cellular health. It is widely known that a diverse group of proteins, called molecular chaperones, function to promote proper folding of other proteins and prevent aggregation. In contrast, intrinsically disordered proteins (IDPs) lack substantial tertiary structures, but nonetheless serve important functional roles. In some cases, IDPs have been observed to display remarkably chaperone-like activities, where they stabilize the activities of client proteins and prevent their aggregation. While it was previously thought that chaperone-like IDPs were mainly utilized by extremophilic organisms in their survival of extreme stress, we recently showed that a group of chaperone-like IDPs, we named heat-resistant obscure (Hero) proteins, are also widespread in non-extremophile animals, including humans and flies. Thus, we should consider the possibility that IDPs serve significant chaperone-like functions in protein stabilization relevant to physiological conditions. However, as most of our understanding of how chaperones function is based on insights from their structured domains, it is unclear how chaperone-like IDPs elicit chaperone-like effects without these structures. Here we summarize our understanding of Hero proteins to date and, based on experimental evidence, outline the features that are likely important for their protein stabilizing activities. We draw on concepts from the studies of chaperones and chaperone-like IDPs, in order to draft potential models of how chaperone-like IDPs achieve chaperone-like effects in the absence of well-defined structures.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130786"},"PeriodicalIF":2.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pedro Almeida , Inês Alves , Ângela Fernandes , Cláudia Lima , Rui Freitas , Isaac Braga , Jorge Correia , Carmen Jerónimo , Salomé S. Pinho
{"title":"“Mannose glycans as key players in trained immunity: A novel anti-tumoral catalyst”","authors":"Pedro Almeida , Inês Alves , Ângela Fernandes , Cláudia Lima , Rui Freitas , Isaac Braga , Jorge Correia , Carmen Jerónimo , Salomé S. Pinho","doi":"10.1016/j.bbagen.2025.130779","DOIUrl":"10.1016/j.bbagen.2025.130779","url":null,"abstract":"<div><div>Cell wall glycans isolated from microorganisms are long known to provoke strong immune responses piloted by innate immune cell populations, including monocytes, in the context of Trained Immunity (TI). However, the contribution of yeast-derived mannan in the reprogramming of monocytes remains ill-defined. Here, we demonstrated that TI is often accompanied by an altered gene expression profile of selected glycan-binding proteins expressed by monocytes, including DC-SIGN and Dectin-2. Additionally, we showed that mannan, a mannose rich glycan, can trigger an enhanced immune phenotype compatible with TI in healthy monocytes, with glycan-primed cells exhibiting enhanced pro-inflammatory cytokine secretion (TNFα and IL-6) and higher activation (CD86) levels. Furthermore, the glycan-mediated priming of monocytes also imposed alterations to the expression of certain Glycan-Binding Proteins, such as DC-SIGN. Importantly, we established that these mannan-trained immune cells displayed an improved capacity to kill tumor cells <em>in vitro</em>. Lastly, we confirmed that monocytes from non-muscle invasive bladder cancer patients treated with BCG instillations presented a TI phenotype, as was revealed by the higher cytokine production and activation. Altogether, this study lays the foundations for exploiting the immunological potential of glycan-derived pathogens in reprogramming innate immune cells towards an effective anti-tumor immune response.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 5","pages":"Article 130779"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deepika Regmi, Seymour Haque, Md Raza Ul Karim, Aleksander Stanic, Deguo Du
{"title":"Inhibition of amyloid formation of prion fragment (106–128) by polyphenolic compounds","authors":"Deepika Regmi, Seymour Haque, Md Raza Ul Karim, Aleksander Stanic, Deguo Du","doi":"10.1016/j.bbagen.2025.130778","DOIUrl":"10.1016/j.bbagen.2025.130778","url":null,"abstract":"<div><div>Prion diseases are characterized by the self-association and amyloid formation of misfolded prion proteins. Developing effective inhibitors of protein aggregation is critical for therapeutic intervention. In this study, we systematically evaluated a range of polyphenolic compounds as potential inhibitors of amyloid fibril formation of PrP(106–128), a prion fragment crucially involved in prion aggregation and propagation. Our findings demonstrate that the basic aromatic backbone structure of flavone alone is insufficient to inhibit PrP(106–128) amyloid formation. Remarkably, flavone molecules containing adjacent hydroxyl groups on the phenolic B or A ring efficiently inhibited PrP(106–128) fibrillization, whereas compounds lacking vicinal hydroxyl groups were less effective in inhibiting amyloid formation. Epigallocatechin-3-gallate (EGCG) was one of the most potent inhibitors found in this study, with the gallate moiety playing an active role in the inhibitory function. Our findings indicate a structure-dependent inhibition activity of the phenolic small molecules, where the number and positioning of hydroxyl groups on the phenyl ring play a pivotal role in inhibiting the aggregation of the peptide. The auto-oxidation of the catechol or pyrogallol moieties to form quinone structures, followed by their reaction with amino acid side chains of the peptide to form covalent adducts, likely account for the inhibitory activity of these phenolic compounds on PrP(106–128) amyloidogenesis. These results will help the design of novel polyphenolic molecules with optimized structural features as potent inhibitors of amyloid formation of both PrP(106–128) and the full-length prion proteins.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 5","pages":"Article 130778"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irina V. Gorudko , Daria V. Grigorieva , Grigory A. Gusakov , Lyudmila V. Baran , Veronika E. Reut , Ekaterina V. Sak , Ilya V. Baimler , Alexander V. Simakin , Alexey S. Dorokhov , Andrey Yu. Izmailov , Dmitriy A. Serov , Sergey V. Gudkov
{"title":"Rod and spherical selenium nanoparticles: Physicochemical properties and effects on red blood cells and neutrophils","authors":"Irina V. Gorudko , Daria V. Grigorieva , Grigory A. Gusakov , Lyudmila V. Baran , Veronika E. Reut , Ekaterina V. Sak , Ilya V. Baimler , Alexander V. Simakin , Alexey S. Dorokhov , Andrey Yu. Izmailov , Dmitriy A. Serov , Sergey V. Gudkov","doi":"10.1016/j.bbagen.2025.130777","DOIUrl":"10.1016/j.bbagen.2025.130777","url":null,"abstract":"<div><div>The influence of selenium (Se) nanoparticles in the form of rods (SeNrs) and spheres (SeSps), synthesized by laser ablation, on the structural and functional properties of human blood erythrocytes and neutrophils was studied for anticancer activity <em>in vitro</em>. SeNrs and SeSps do not have cytotoxicity towards neutrophils and do not cause hemolysis. The elastic modulus and resistance of erythrocytes to HOCl-induced hemolysis increased after binding of Se nanoparticles to the plasma membrane. The interaction of Se nanoparticles with neutrophils is accompanied by their actin-dependent macropinocytosis, triggering intracellular signaling processes leading to the assembly and activation of NADPH oxidase. Comparative analysis of the effects of SeNrs and SeSps on cells showed that they have similar effects. This may be due to the fact that SeNrs interact with the cell surface with their end faces, and, therefore, have the same initial contact with the plasma membrane as SeSps. However, SeSps and SeNrs showed chronic cytotoxicity after 48 h incubation, indicating the need to find ways to reduce their toxicity further. Further use of Se nanoparticles in anisotropic form in biomedical research for the development of therapeutic agents seems promising.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 5","pages":"Article 130777"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}