{"title":"NSUN6 Maintains BMPER Stability in an m5C-Dependent Manner to Suppress Cell Proliferation and Migration in Hepatocellular Carcinoma","authors":"Chunlin Liu, Yumin Wu, Ying Wu, Weizhi Luo, Yuefei Hong, Leichang Jiang, Senrui Wang, Duanming Du","doi":"10.1111/boc.70023","DOIUrl":"https://doi.org/10.1111/boc.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The expression of Nop2/Sun domain family member 6 (NSUN6), an RNA m5C methyltransferase, is correlated with the prognosis of various cancers. However, its role in the progression of hepatocellular carcinoma (HCC) remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of NSUN6 was analyzed using the TCGA-HCC cohort, as well as through quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting in tumor tissues from HCC patients and various HCC cell lines. Moreover, its biological functions were detected using cell counting kit 8 (CCK8), colony formation, 5-ethynyl-2′-deoxyuridine (EdU), wound healing, and transwell invasion assays in vitro, as well as in an HCC patient-derived xenograft (PDX) mouse model in vivo. The molecular mechanism underlying NSUN6 was explored using methylated RNA immunoprecipitation sequencing (MeRIP-seq), double luciferase reporter gene assay, actinomycin-D assay, and rescue experiments in SNU449 cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression level of NSUN6 was significantly decreased in the TCGA-HCC cohort, tumor tissues of HCC patients and HCC cell lines. NSUN6 overexpression markedly inhibited the proliferative and migratory abilities of HCC cells in the PDX mouse model. Additionally, BMPER was identified as a downstream target of NSUN6, while NSUN6 could stabilize BMPER expression in an m5C-dependent manner. Finally, BMPER knockdown reversed the positive effects of NSUN6 in suppressing HCC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study elucidated the inhibitory effect of NSUN6 overexpression in HCC development, with BMPER identified as a downstream target of NSUN6. NSUN6 regulates BMPER expression in an m5C-dependent manner, thereby influencing HCC progression. Overall, these results suggest that the NSUN6/BMPER axis may serve as a potential therapeutic target for HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520268","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}
Robert Hromas, Austin Kirby, Andrew Carrillo, Aruna Jasiwal, Kimi Kong, Manh Tien Tran, Dominic Arris, Elizabeth A. Williamson
{"title":"The DNA Repair Component EEPD1 Regulates Actin Polymerization","authors":"Robert Hromas, Austin Kirby, Andrew Carrillo, Aruna Jasiwal, Kimi Kong, Manh Tien Tran, Dominic Arris, Elizabeth A. Williamson","doi":"10.1111/boc.70022","DOIUrl":"https://doi.org/10.1111/boc.70022","url":null,"abstract":"<p>Endonuclease exonuclease phosphatase domain-containing protein 1 (EEPD1) is a DNase1 superfamily member that has DNA endonuclease activity. It plays a critical role in multiple DNA repair processes such as oxidative damage repair and stressed replication fork repair. Interestingly, EEPD1 is myristoylated and palmitoylated near its amino terminus in response to high levels of cholesterol, and this localizes EEPD1 protein to the inner cell membrane. Surprisingly, we found that EEPD1 promotes cortical branching actin polymerization and proper lamellipodia formation and is necessary for subsequent cell migration. EEPD1's enhancement of actin polymerization partially required its myristoylation and palmitoylation. EEPD1 depletion also resulted in marked abnormalities in nuclear morphology. Loss of EEPD1 resulted in loss of phosphorylation of SRC, RAC1, cortactin, and profilin, which are essential steps in signaling for actin polymerization. Loss of EEPD1 lowered SRC kinase activity, which would harm actin polymerization. In summary, EEPD1 is a novel, positive regulator of the signaling pathway for actin polymerization, linking actin regulation to nuclear morphology and DNA repair.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520307","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}
{"title":"In Toto Adipocytes Analysis Using Hydrophilic Tissue Clearing, Light Sheet Microscopy, and Deep Learning-Based Image Processing","authors":"Dylan Le Jan, Manar Harb, Mohamed Siliman Misha, Jean-Claude Desfontis, Yassine Mallem, Laurence Dubreil","doi":"10.1111/boc.70013","DOIUrl":"https://doi.org/10.1111/boc.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Obesity is a multifactorial metabolic disease characterized by excessive fat storage in adipocytes, particularly in visceral adipose tissue (VAT) like mesenteric adipocytes. Metabolic dysfunctions due to obesity are often associated with modification of adipocyte volume. Various techniques for measuring adipocyte size are described in the literature, including classical histological methods on paraffin-embedded tissue sections or dissociation of adipose tissue (AT) using collagenase with artifacts due to AT post treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study aims to develop and implement an innovative method for 3D investigation of AT to assess adipocyte volume, overcoming the limitations and biases inherent in traditional techniques. The principle of the method relies on fluorescent labeling of lipids and extracellular matrix (ECM) in toto within AT, followed by a tissue clearing step without delipidation and imaging using 3D light sheet microscopy coupled with automated analysis of adipocyte size through a deep learning approach. By this work we showed that the volume of adipocytes increased in mesenteric AT from obese rats with an increase in the distance between adipocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Significance</h3>\u0000 \u0000 <p>The current work highlights the interest in combining AT clearing without a delipidation step and light sheet microscopy for in toto 3D adipocyte characterization in obese versus healthy rats. While this method is particularly valuable for understanding adipocyte hypertrophy in the context of obesity, its applicability extends beyond this area. This innovative approach offers valuable opportunities for investigating adipocyte dynamics in various pathological conditions, evaluating the impact of nutritional interventions, and assessing the effectiveness of pharmacological treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339242","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}
Mahsa Kheradmandi, Amir M. Farnoud, Monica M. Burdick
{"title":"Investigating the Role of Proteins and Lipids in the Prevention of Nanoparticle-Induced Cellular Membrane Damage Using Engineered Biomimetic Vesicles","authors":"Mahsa Kheradmandi, Amir M. Farnoud, Monica M. Burdick","doi":"10.1111/boc.70020","DOIUrl":"https://doi.org/10.1111/boc.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although nanoparticles are promising tools for novel therapeutics, there is a need to better understand different mechanisms of cellular nanotoxicity. Several studies have investigated the intracellular cytotoxicity of nanoparticles after entering cells via endocytosis, but the impact on the plasma membrane remains unclear. Giant plasma membrane vesicles (GPMVs) serve as powerful models to study nanoparticle–membrane interactions while preserving the native lipid and protein composition, and eliminating endocytosis interference. This study focuses on understanding the mechanism underlying the disruptive effects of nanoparticles on the cell membrane using biomimetic GPMVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A549 cells were chemically induced to generate GPMVs. GPMV-like, protein-free vesicles were also synthesized to understand the role of membrane proteins in nanotoxicity. Lipid exchange was then employed to investigate the function of lipids in membrane integrity. These vesicles were utilized to study the mechanisms of nanoparticle–membrane cytotoxicity. Additionally, this study introduced a novel repairing method that utilizes surface engineering and chemical alterations to reconstruct the pores formed during vesiculation, offering a new method to enhance the stability of biomembranes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study is the first to demonstrate that membrane proteins significantly enhance the ability of biomembranes to interact and adsorb silica nanoparticles. Additionally, nanoparticle exposure induced more morphological damages in the protein-free compared to the protein-containing GPMVs. Furthermore, the exchange with glycerophospholipids containing one saturated acyl chain significantly improved the stability and fluidity of vesicles before and after exposure to different toxic nanoparticles. This work successfully introduces a new repairing technique for the loaded vesicles derived directly from the living cells to enhance the encapsulation efficiency and minimize the nanotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, membrane lipid saturation and selective protein incorporation are critical factors in nanoparticle binding, vesicle stability, and exogenously induced disruption of membrane-derived vesicles. These findings provide new insights into minimizing nanotoxicity while optimizing nanoparticle-based therapeutic applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339243","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}
Mireia Gomez Duro, Lucas Alves Tavares, Izadora Peter Furtado, Julien Saint-Pol, Gisela D'Angelo
{"title":"Protrusion-Derived Extracellular Vesicles (PD-EVs) and Their Diverse Origins: Key Players in Cellular Communication, Cancer Progression, and T Cell Modulation","authors":"Mireia Gomez Duro, Lucas Alves Tavares, Izadora Peter Furtado, Julien Saint-Pol, Gisela D'Angelo","doi":"10.1111/boc.70018","DOIUrl":"https://doi.org/10.1111/boc.70018","url":null,"abstract":"<p>Protrusion-derived extracellular vesicles (PD-EVs) are a specialized subset of extracellular vesicles (EVs) generated from dynamic cellular extensions. These structures play a crucial role in cellular communication and have emerged as pivotal mediators in various biological processes, including cancer progression and immune modulation. In cancer, PD-EVs facilitate tumor growth, invasion, and metastasis by delivering oncogenic cargo that remodels the tumor microenvironment, promotes angiogenesis, and supports immune evasion. They are also implicated in establishing pre-metastatic niches and enabling cancer cells to colonize distant organs. PD-EVs are characterized by a distinct molecular signature linked to their origin from specialized plasma membrane domains. Their unique composition makes them promising biomarkers for early cancer detection, disease monitoring, metastatic potential assessment, and therapeutic response evaluation. Targeting PD-EV biogenesis, release, or uptake represents a novel therapeutic strategy to disrupt tumor progression and overcome resistance to current treatments. However, distinguishing PD-EVs from other EV subtypes remains challenging due to overlapping characteristics. This review consolidates the latest evidence on PD-EVs, focusing on their biogenesis, limitations in their study, functional roles in cancer, and potential applications in diagnostics and therapeutics, especially concerning immune modulation and T-cell activation.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264509","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}
Michael Okafor, David Schmitt, Stéphane Ory, Stéphane Gasman, Christelle Hureau, Peter Faller, Nicolas Vitale
{"title":"The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides","authors":"Michael Okafor, David Schmitt, Stéphane Ory, Stéphane Gasman, Christelle Hureau, Peter Faller, Nicolas Vitale","doi":"10.1111/boc.70012","DOIUrl":"https://doi.org/10.1111/boc.70012","url":null,"abstract":"<p>The cell plasma membrane acts as a semi-permeable barrier essential for cellular protection and function, posing a challenge for therapeutic molecule delivery. Conventional techniques for crossing this barrier, including biophysical and biochemical methods, often exhibit limitations such as cytotoxicity and the risk of genomic integration when viral vectors are involved. In contrast, cell-penetrating peptides (CPPs) offer a promising non-invasive means to deliver a broad range of molecular cargoes, including proteins, nucleic acids and small molecules, into cells. CPPs, typically 5 to 30 amino acids long and rich in basic or non-polar residues, interact favourably with different cell membranes. These peptides have evolved since the discovery of the HIV-1 TAT peptide in the 1980s, expanding into various CPP families with diverse therapeutic applications. CPPs can form covalent or non-covalent complexes with their cargo, influencing their stability and efficacy. Based on their sequence properties and interactions, CPPs can be amphipathic or non-amphipathic, with distinct mechanisms of membrane penetration, such as direct penetration and endocytosis. While their uptake mechanisms are complex and not fully elucidated, ongoing optimization aims to enhance CPP specificity and efficacy. CPPs have demonstrated potential in drug delivery, gene therapy, cancer treatment and vaccine development, addressing key safety and efficiency concerns associated with viral vectors. This review explores the classification, mechanisms of action and therapeutic potential. It focuses on the intracellular vesicular trafficking of CPPs, highlighting their role as transformative tools in advancing cellular therapies and medical treatments.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244266","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}
{"title":"Correction to “How Intercellular Forces Regulate Cell Competition”","authors":"","doi":"10.1111/boc.70019","DOIUrl":"https://doi.org/10.1111/boc.70019","url":null,"abstract":"<p>A. Schoenit, S. Monfared, L. Anger, et al., “How Intercellular Forces Regulate Cell Competition,” <i>Biology of the Cell</i> 117 (2025): e70004, https://doi.org/10.1111/boc.70004</p><p>The article title has been updated from “Force transmission is a master regulator of mechanical cell competition” to “How intercellular forces regulate cell competition” to avoid confusion with the original paper it refers to.</p><p>We apologize for this error.</p><p></p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244268","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}
Morgane Rodriguez, Valérie Simon, Bénédicte Delaval, Benjamin Vitre
{"title":"An Auxin Inducible Degradation System to Study Mklp2 Functions in MDCK Epithelial Cells","authors":"Morgane Rodriguez, Valérie Simon, Bénédicte Delaval, Benjamin Vitre","doi":"10.1111/boc.70015","DOIUrl":"https://doi.org/10.1111/boc.70015","url":null,"abstract":"<p>The auxin inducible degradation (AID) system, which allows for rapid and inducible degradation of a protein of interest, is an efficient technology to study protein function in cells. This system proves particularly useful to study cellular motors that can be involved in different mechanisms depending on the cell cycle stage. Mitotic kinesin-like protein 2 (Mklp2) is a member of the kinesin-6 family involved in intracellular trafficking both in interphase and mitosis. In mitosis, at anaphase onset, it relocates the chromosomal passenger complex (CPC), from the chromatin to the spindle midzone and equatorial cortex. Inhibition or knockdown of Mklp2 therefore leads to CPC re-localization defects and cytokinesis failure. Existing tools used to study Mklp2 functions in cells, including antibodies, siRNA, and small molecule inhibitors, allowed the identification of the general function of Mklp2 in mitosis. However, these tools induce different intermediate phenotypes during the course of mitosis, highlighting the need for an alternative Mklp2 perturbation approach. We report here a new tool to study the discrete localization of endogenous Mklp2 at different stages of the cell cycle combined with an AID tag that allows the study of the kinesin with high specificity, high efficiency, and high temporal resolution in MDCK (Madin-Darby canine kidney) epithelial cells. We show that upon auxin treatment, the acute and rapid degradation of Mklp2 results in delayed re-localization of CPC component Aurora-B to the spindle midzone during anaphase, cytokinesis failure, and cell binucleation. We validate the specificity of the system by rescuing Mklp2 expression and reversing the phenotypes. Overall, this new tool facilitates the study of endogenous Mklp2 localization and function at specific stages of the cell cycle and offers a highly specific method for exploring its roles in a nontransformed mammalian model cell line widely used to study epithelial organization and dynamics.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244267","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}
{"title":"Chromosome Segregation in Closed Mitosis Under an Excess of Nuclear Envelope","authors":"Noelia Rodríguez-Herrera, Silvia Santana-Sosa, Sara Medina-Suárez, Samantha Morais-Armas, Emiliano Matos-Perdomo, Félix Machín","doi":"10.1111/boc.70011","DOIUrl":"https://doi.org/10.1111/boc.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Two major types of cell division occur in eukaryotic cells regarding the dismantlement or not of the nuclear envelope (NE) in mitosis, open and closed mitosis, respectively. In the budding yeast <i>Saccharomyces cerevisiae</i>, the prototypical model for closed mitosis, the Nem1-Spo7 phosphatase complex, which regulates lipid metabolism, plays a key role in coordinating NE expansion throughout the cell cycle. Indeed, Nem1 depletion leads to abnormal NE evaginations in interphase, which protrude the ribosomal DNA (rDNA) and the nucleolus. However, the specific impact of these NE and chromosome organization abnormalities during chromosome segregation in anaphase remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study investigated chromosome segregation and NE dynamics during closed mitosis in relation to the presence or absence of Nem1. Nem1 was depleted by means of the auxin degron system. Nem1 depletion led to the formation of chromatin protrusions in interphase, particularly at the rDNA locus, as it has been reported before for <i>nem1</i> mutants. These protrusions persisted into anaphase and were associated with delayed recoiling of the rDNA-bearing chromosome XII right arm, resulting in lagging chromatin during late anaphase. Additionally, cells can maintain nucleus-vacuole junctions (NVJs) during anaphase, suggesting that vacuoles may play a role in shaping NE morphology during chromosome segregation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that the Nem1-Spo7/lipin regulation of the NE size is crucial for the timely segregation of the rDNA-bearing chromosome during closed mitosis. Thus, the NE homeostasis actively contributes to chromosome segregation and the spatial organization of chromosomes in subsequent cell cycles. In addition, the persistent association between the NE and vacuoles in anaphase further underscores how cumbersome organelle interactions can become during closed mitosis, opening inspiring research avenues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091591","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}
Ashish Agrahari, Km. Archana, Nittu Singh, Akshay Joshi, Budai S. Vivek Vinod, Sourav Haldar, Krishan Gopal Thakur, Raj Kamal Tripathi
{"title":"Identification and Characterization of a Novel Protein–Protein Interaction Among SARS-CoV-2 Nucleocapsid, Host SFPQ, and hnRNP U and Its Potential Role in Virus Replication","authors":"Ashish Agrahari, Km. Archana, Nittu Singh, Akshay Joshi, Budai S. Vivek Vinod, Sourav Haldar, Krishan Gopal Thakur, Raj Kamal Tripathi","doi":"10.1111/boc.70008","DOIUrl":"https://doi.org/10.1111/boc.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>SARS-CoV-2 has led to significant global health and economic challenges and caused the COVID-19 pandemic. The ability of the virus to replicate adeptly within host cells is critical for its pathogenicity. The structural nucleocapsid (N) protein of SARS-CoV-2 packages newly synthesized viral RNA with the association of various host proteins that may contribute to different functions in maintaining a productive viral life cycle. In this study, we report the identification and characterization of host proteins SFPQ and hnRNP U interacting with SARS-CoV-2 N protein in both N-transfected cells and virus-infected cells, forming a hetero-trimeric protein complex. Using carefully designed peptides that span the length of N protein and competitive inhibition, we identified the interacting domains at N protein that interact with SFPQ and hnRNP U. Our results constitute the first report that the characterized N protein and host SFPQ and hnRNP U form a hetero-trimeric protein complex in both N transfected cells and virus-infected cells. Utilizing competitive peptides, we were able to disrupt the hetero-trimeric protein complex in virus-infected cells, leading to reduction in viral replication. These results clearly demonstrate that N-SFPQ-hnRNP U hetero-trimeric protein complex formation is found in SARS-CoV-2 infected cells that regulate viral replication. Our findings suggest that the protein–protein interaction (PPI) between N-SFPQ-hnRNP U hetero-trimeric protein complexes could be a novel drug target for developing therapeutics against COVID-19.</p>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857104","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}