The EMBO Journal最新文献_第5页

T-cell protrusions enable fast, localised initiation of chimeric antigen receptor signalling. t细胞突起能够快速、局部地启动嵌合抗原受体信号传导。

The EMBO Journal Pub Date : 2026-04-21 DOI: 10.1038/s44318-026-00773-5

Carmen Rodilla-Ramirez,Giorgia Carai,Eleanor Fox,Amin Zehtabian,Helen Adam,Katja Dallio,Pia Lazki-Hagenbach,Helge Ewers,Xiaolei Su,Francesca Bottanelli

{"title":"T-cell protrusions enable fast, localised initiation of chimeric antigen receptor signalling.","authors":"Carmen Rodilla-Ramirez,Giorgia Carai,Eleanor Fox,Amin Zehtabian,Helen Adam,Katja Dallio,Pia Lazki-Hagenbach,Helge Ewers,Xiaolei Su,Francesca Bottanelli","doi":"10.1038/s44318-026-00773-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00773-5","url":null,"abstract":"Actin-rich protrusions densely cover the surface of T cells and are well characterised for their role in migration. Recent studies have uncovered their contribution to antigen surveillance and immune signalling. To further explore how protrusions initiate signalling pathways mediating T-cell activation, we performed live-cell imaging of endogenously tagged proteins in HER2-specific chimeric antigen receptor (CAR) T cells targeting HER2⁺ breast-cancer cells. Quantitative STED microscopy allowed us to monitor protein rearrangement and to correlate it with membrane topology over time. Before activation, key signalling proteins (including Lck, CD45, LAT, and the CAR) were not enriched in protrusions. Upon contact with target cells, rapid protein reorganisation occurred preferentially within protrusions, initiating signalling. HER2-CAR clustering, accompanied by ZAP-70 and LAT recruitment, was enhanced in protrusions. While Lck distribution remained unchanged, exclusion of the phosphatase CD45 was enhanced at protrusion-cell contacts, independently of the CAR signalling domain. Overall, signalling machinery rearranged faster and more effectively at protrusive contacts than at main plasma membrane regions. Together, our data re-frame protrusions as sites of enhanced receptor activation by exclusion and clustering dynamics rather than by pre-enrichment of the signalling machinery.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"135 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic blebbing and absence of organelle transfer during mouse oocyte formation. 小鼠卵母细胞形成过程中的动态气泡和细胞器转移缺失。

The EMBO Journal Pub Date : 2026-04-21 DOI: 10.1038/s44318-026-00780-6

Eishi Aizawa,So Shimamoto,Eriko Kajikawa,Junko Hara,Takaya Abe,Hiroki Shibuya,Tomoya S Kitajima

{"title":"Dynamic blebbing and absence of organelle transfer during mouse oocyte formation.","authors":"Eishi Aizawa,So Shimamoto,Eriko Kajikawa,Junko Hara,Takaya Abe,Hiroki Shibuya,Tomoya S Kitajima","doi":"10.1038/s44318-026-00780-6","DOIUrl":"https://doi.org/10.1038/s44318-026-00780-6","url":null,"abstract":"Oocyte formation in mammals is a tightly regulated process essential for female fertility, yet the underlying mechanisms remain poorly understood. In this study, we establish an ex vivo culture system that faithfully recapitulates in vivo development and enables long-term live imaging of mouse fetal ovaries. Using high resolution imaging, we capture the dynamic behaviors of germ cells during the development from oogonia to nascent oocytes. We identify pronounced blebbing activity during the mitosis-to-meiosis transition. This behavior is regulated by meiotic initiation signals, underscoring its potential developmental relevance, although its precise role remains unclear. A prevailing model suggests that oocyte formation involves organelle transfer from neighboring germ cells during cyst breakdown. However, through photoconversion-based tracking, we observe no detectable transfer of mitochondria or centrosomes, as organelles remain confined to individual cells. These findings point to alternative mechanisms for cytoplasmic enrichment in oocytes. Our study provides new insights into mammalian oocyte formation and establishes a powerful platform for analyzing germ cell dynamics in real time.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation. CD20尾部通过PKCδ磷酸化与14-3-3/GEF-H1复合物和微管网络相互作用。

The EMBO Journal Pub Date : 2026-04-17 DOI: 10.1038/s44318-026-00781-5

Kathrin Kläsener,Cindy Eunhee Lee,Julian Bender,Angela Naumann,Lena Reimann,Geoffroy Andrieux,Claudio Mussolino,Nadja Herrmann,Roland Nitschke,Reinhard E Voll,Bettina Warscheid,Klaus Warnatz,Michael Reth

{"title":"CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation.","authors":"Kathrin Kläsener,Cindy Eunhee Lee,Julian Bender,Angela Naumann,Lena Reimann,Geoffroy Andrieux,Claudio Mussolino,Nadja Herrmann,Roland Nitschke,Reinhard E Voll,Bettina Warscheid,Klaus Warnatz,Michael Reth","doi":"10.1038/s44318-026-00781-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00781-5","url":null,"abstract":"CD20 is a four-helix transmembrane protein specifically expressed in B-cells that serves as a prominent target of therapeutic anti-CD20 antibodies. It is localized in a membrane nanocluster harboring the B-cell antigen receptor of IgD class (IgD-BCR), where it functions to maintain the resting state of naïve B-lymphocytes. How CD20 exerts this resting B-cell gatekeeper function is not yet known. Using Ramos and human peripheral blood B-cells, we show here that the serine/threonine kinase PKCδ constitutively phosphorylates serine residues in the two cytosolic tails of CD20. Phosphorylated CD20 becomes a binding target for 14-3-3 adaptor proteins, which link it to the RhoA GDP/GTP exchange factor GEF-H1 and the microtubule network, supporting the function of the IgD-BCR nanocluster. Binding of anti-CD20 antibodies results in microtubule dissociation and replacement of the GEF-H1/CD20 complex with a RhoA-GTP/ROCK1/CD20 complex, which promotes actomyosin contractility. Our study suggests that CD20 not only maintains the resting state of B-lymphocytes by anchoring the microtubule network and controlling the stability of the IgD-BCR nanocluster, but also mediates the microtubule/actin switch in active B-lymphocytes. These findings could have important implications for anti-CD20 antibody treatment and the optimization of therapeutic protocols.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"242 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interferon-γ selectively promotes survival of alveolar progenitor cells in a human lung organoid model. 干扰素-γ选择性促进人肺类器官模型中肺泡祖细胞的存活。

The EMBO Journal Pub Date : 2026-04-16 DOI: 10.1038/s44318-026-00774-4

Antonella F M Dost,Katarína Balážová,Carla Pou Casellas,Lisanne M van Rooijen,Wisse Epskamp,Gijs J F van Son,Willine J van de Wetering,Carmen Lopez-Iglesias,Harry Begthel,Peter J Peters,Niels Smakman,Johan H van Es,Hans Clevers

{"title":"Interferon-γ selectively promotes survival of alveolar progenitor cells in a human lung organoid model.","authors":"Antonella F M Dost,Katarína Balážová,Carla Pou Casellas,Lisanne M van Rooijen,Wisse Epskamp,Gijs J F van Son,Willine J van de Wetering,Carmen Lopez-Iglesias,Harry Begthel,Peter J Peters,Niels Smakman,Johan H van Es,Hans Clevers","doi":"10.1038/s44318-026-00774-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00774-4","url":null,"abstract":"Disease of the lung alveoli is frequently associated with acute or chronic inflammation. At present, there are no effective therapies to support regeneration of the alveolar epithelium, and ongoing inflammation adds an additional layer of complexity to many lung diseases. Here, we describe a primary adult human organoid model for investigating how inflammation shapes alveolar regeneration. Unlike previous models, this system supports long-term expansion of newly identified human-specific alveolar progenitor cells and serum-free differentiation into alveolar type 1 (AT1)-like cells. Using this platform, we find that interferon-gamma (IFN-γ) exerts cytotoxic effects on mature AT1-like cells while promoting survival of alveolar progenitor cells mediated by BIRC3. This unexpected selective positive effect of IFN-γ on alveolar progenitors underscores the need for nuanced and context-dependent evaluation of the influence of pro-inflammatory cytokines on alveolar regeneration. Our organoid model provides a reductionist platform for mechanistic studies and discovery of strategies to enhance alveolar regeneration.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects. 人类胰岛的深度单细胞解码揭示了T2D β细胞基因表达缺陷。

The EMBO Journal Pub Date : 2026-04-15 DOI: 10.1038/s44318-026-00744-w

Khushdeep Bandesh,Efthymios Motakis,Siddhi Nargund,Romy Kursawe,Vijay Selvam, Ansarullah,Redwan M Bhuiyan,Giray Naim Eryilmaz,Amelia M Willett,Jacqueline K White,Sai Nivedita Krishnan,Cassandra N Spracklen,Duygu Ucar,Michael L Stitzel

{"title":"Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.","authors":"Khushdeep Bandesh,Efthymios Motakis,Siddhi Nargund,Romy Kursawe,Vijay Selvam, Ansarullah,Redwan M Bhuiyan,Giray Naim Eryilmaz,Amelia M Willett,Jacqueline K White,Sai Nivedita Krishnan,Cassandra N Spracklen,Duygu Ucar,Michael L Stitzel","doi":"10.1038/s44318-026-00744-w","DOIUrl":"https://doi.org/10.1038/s44318-026-00744-w","url":null,"abstract":"Pancreatic islets maintain glucose homeostasis through coordinated action of endocrine and affiliate cell types and are central to type 2 diabetes (T2D) genetics and pathophysiology. Our understanding of robust human islet cell type-specific alterations in T2D remains limited. Here, we report comprehensive single-cell transcriptome profiling of 245,878 human islet cells from 48 donors spanning non-diabetic, pre-diabetic, and T2D states, and we identify 14 distinct cell types detected in every donor. Cell-cluster analysis reveals ~25-30% β-cell reductions consisting of β-cell loss and proportional increases in a senescent β-cell subpopulation in T2D donors, consistent with previous reports. Further, comparative data integration identifies 511 differentially expressed genes (DEGs) in T2D β-cells, including T2D-associated vitamin A metabolism genes, which are linked to impaired β-cell viability by multimodal functional validation. Integration with T2D genetic, proteomic, and mouse model metabolic phenotypes nominates 58 candidate causal T2D genes, including PDZK1 and GRAMD2B, which preserve β-cell mass. Together, this genomic resource provides an enhanced type 2 diabetes expression-atlas for data exploration, analysis, and hypothesis testing, as well as a novel genomic resource for insights into T2D pathophysiology and human islet dysfunction.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosomal instability promotes cell migration and invasion via EFEMP1 secretion into extracellular vesicles. 染色体不稳定性通过EFEMP1分泌到细胞外囊泡促进细胞迁移和侵袭。

The EMBO Journal Pub Date : 2026-04-13 DOI: 10.1038/s44318-026-00766-4

Siqi Zheng,Ruifang Tian,Marsudi Siburian,Anna Haider Rubio,Yuanyuan Liu,Rene Wardenaar,Marjan Shirzai,Laura Kempe,Emma Dijkstra,Eliza Warszawik,Maria Suarez Peredo Rodriguez,Klaas Sjollema,Petra L Bakker,Patrick van Rijn,Michaela Borghesan,Judith Tml Paridaen,Stefano Santaguida,Floris Foijer

{"title":"Chromosomal instability promotes cell migration and invasion via EFEMP1 secretion into extracellular vesicles.","authors":"Siqi Zheng,Ruifang Tian,Marsudi Siburian,Anna Haider Rubio,Yuanyuan Liu,Rene Wardenaar,Marjan Shirzai,Laura Kempe,Emma Dijkstra,Eliza Warszawik,Maria Suarez Peredo Rodriguez,Klaas Sjollema,Petra L Bakker,Patrick van Rijn,Michaela Borghesan,Judith Tml Paridaen,Stefano Santaguida,Floris Foijer","doi":"10.1038/s44318-026-00766-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00766-4","url":null,"abstract":"Triple-negative breast cancer (TNBC) is characterised by high rates of chromosomal instability (CIN) and rewired intercellular communication driven by both soluble factors and extracellular vesicles (EVs). To assess how CIN might affect EV-mediated signalling in TNBC, we studied the EV landscape of TNBC cell lines with induced CIN. We find that CIN leads to increased secretion of EVs and that these EVs promote cell migration of recipient cells. EVs are enriched for extracellular matrix (ECM) proteins, including EFEMP1. Indeed, modulation of EFEMP1 levels in EVs significantly alters migration behaviour of EV-treated cells. We show that EFEMP1 expression is regulated by STAT1, that EVs from STAT1-deficient cells no longer promote migration, and that this can be rescued by overexpression of EFEMP1 in STAT1-null cells. Xenografting TNBC cells with EFEMP1-enriched cells promotes migration in zebrafish embryos, suggesting that EFEMP1 expression is a factor that promotes metastasis. Together, our results identify a CIN-associated EV program in triple-negative breast cancer and highlight EFEMP1 as a potential therapeutic target to impair EV-driven tumour cell migration.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating the protein interaction network of one of the largest icosahedral capsids in the virosphere. 阐明病毒圈中最大的二十面体衣壳之一的蛋白质相互作用网络。

The EMBO Journal Pub Date : 2026-04-10 DOI: 10.1038/s44318-026-00770-8

Hela Safi,Alain Schmitt,Alwena Tollec,Lucid Belmudes,Agathe M G Colmant,Olivier Poirot,Sebastien Santini,Matthieu Legendre,Yohann Couté,Hugo Bisio,Chantal Abergel

{"title":"Elucidating the protein interaction network of one of the largest icosahedral capsids in the virosphere.","authors":"Hela Safi,Alain Schmitt,Alwena Tollec,Lucid Belmudes,Agathe M G Colmant,Olivier Poirot,Sebastien Santini,Matthieu Legendre,Yohann Couté,Hugo Bisio,Chantal Abergel","doi":"10.1038/s44318-026-00770-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00770-8","url":null,"abstract":"Giant viruses challenge traditional boundaries of virology with their large particle sizes, complex genomes, and unique replication strategies. Yet, despite its 750 nm diameter and incorporation of dozens of proteins, the mimivirus virion retains an icosahedral symmetry, a trait often associated with smaller viruses. The functional roles and interactions of most proteins composing such complex icosahedral particles remain elusive. Here, we dissect the spatial and functional organization of mimivirus morphogenesis by integrating bioinformatics, genetics, and interactomics. We performed protein clustering using a structure-informed approach, integrating AlphaFold models with sequence information, to classify and functionally annotate the orphan-protein-rich mimivirus proteome. To map the protein-protein interaction network during morphogenesis, we employed endogenous tagging and co-immunoprecipitation coupled to mass spectrometry. This strategy revealed distinct interaction modules associated with the virion membrane, nucleoid, and viral factory compartments. Comparative analyses with other icosahedral and non-icosahedral giant viruses uncovered conserved assembly nodes and virion-shape-specific adaptations. Our findings shed light on the global organization of mimivirus virion biogenesis and highlight the evolutionary plasticity of viral morphogenetic networks within the Nucleocytoviricota.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The H3K36me3 methyltransferase SETD2 contributes to PAF1C interactions with RNA Pol II and is required for neuronal differentiation. H3K36me3甲基转移酶SETD2有助于PAF1C与RNA Pol II的相互作用，并且是神经元分化所必需的。

The EMBO Journal Pub Date : 2026-04-10 DOI: 10.1038/s44318-026-00768-2

Christina Ambrosi,Ramon Pfaendler,Kristeli Eleftheriou,Stefan Butz,Davide Recchia,Xue Bao,Richard Cardoso da Silva,Niklas Kupfer,Ilse M Lagerwaard,Hanneke Vlaming,Nina Schmolka,Vivek Bhardwaj,Tuncay Baubec

引用次数: 0

SenSet defines cell-type specific senescence signatures in the aged human lung. SenSet定义了老年人肺中细胞类型特异性衰老特征。

The EMBO Journal Pub Date : 2026-04-10 DOI: 10.1038/s44318-026-00762-8

Euxhen Hasanaj,Delphine Beaulieu,Cankun Wang,Qianjiang Hu,Lorena Rosas,Marta Bueno,John C Sembrat,Ricardo H Pineda,Maria Camila Melo-Narvaez,Nayra Cardenes,Zhao Yanwu,Zhang Yingze,Robert Lafyatis,Alison Morris,Ana Mora,Mauricio Rojas,Dongmei Li,Irfan Rahman,Gloria S Pryhuber,Mareike Lehmann,Jonathan Alder,Aditi Gurkar,Toren Finkel,Qin Ma,Jose Lugo-Martinez,Barnabás Póczos,Ziv Bar-Joseph,Oliver Eickelberg,Melanie Königshoff

{"title":"SenSet defines cell-type specific senescence signatures in the aged human lung.","authors":"Euxhen Hasanaj,Delphine Beaulieu,Cankun Wang,Qianjiang Hu,Lorena Rosas,Marta Bueno,John C Sembrat,Ricardo H Pineda,Maria Camila Melo-Narvaez,Nayra Cardenes,Zhao Yanwu,Zhang Yingze,Robert Lafyatis,Alison Morris,Ana Mora,Mauricio Rojas,Dongmei Li,Irfan Rahman,Gloria S Pryhuber,Mareike Lehmann,Jonathan Alder,Aditi Gurkar,Toren Finkel,Qin Ma,Jose Lugo-Martinez,Barnabás Póczos,Ziv Bar-Joseph,Oliver Eickelberg,Melanie Königshoff","doi":"10.1038/s44318-026-00762-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00762-8","url":null,"abstract":"Cellular senescence is defined as an irreversible growth arrest observed when cells are exposed to a variety of stressors, including DNA damage, oxidative stress, or nutrient deprivation. Although senescence is a well-established driver of aging and age-related diseases, it is a highly heterogeneous process with significant variations across organisms, tissues, and cell types. The relatively low abundance of senescent cells in healthy aged tissues poses a major challenge to the longitudinal study of senescence in specific organs, including the human lung. To overcome this limitation, we developed a positive-unlabeled learning framework to generate a comprehensive list of senescence marker genes in human lungs (termed SenSet) using the largest publicly available single-cell lung dataset, the Human Lung Cell Atlas (HLCA). We validated SenSet in a highly complex ex vivo human 3D lung tissue culture model subjected to the senescence inducers bleomycin, doxorubicin, or irradiation, and established its sensitivity and accuracy in characterizing senescence. Using SenSet, we identified and validated cell-type-specific senescence signatures in distinct lung cell populations upon aging and environmental exposure. Our study provides a comprehensive analysis of senescent cells in the healthy aging lung, presenting fundamental implications for our understanding of major lung diseases, including cancer, fibrosis, chronic obstructive pulmonary disease, or asthma.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global stabilization of the transcriptome in mitotic cells. 有丝分裂细胞中转录组的全局稳定。

The EMBO Journal Pub Date : 2026-04-09 DOI: 10.1038/s44318-026-00765-5

Ekaterina Khalizeva,Arash Latifkar,Kehui Xiang,David P Bartel,Jimmy Ly,Iain M Cheeseman

{"title":"Global stabilization of the transcriptome in mitotic cells.","authors":"Ekaterina Khalizeva,Arash Latifkar,Kehui Xiang,David P Bartel,Jimmy Ly,Iain M Cheeseman","doi":"10.1038/s44318-026-00765-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00765-5","url":null,"abstract":"In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique aspects of mitosis require substantial adaptations to gene expression. During interphase, homeostatic control of mRNA levels involves a constant balance of transcription and degradation, with a median mRNA half-life of ~2-4 h. If such short half-lives persisted in mitosis, cells would be expected to rapidly deplete their transcriptome without new transcription. Here, we report that the transcriptome is globally stabilized during prolonged mitotic delays. Median mRNA half-lives are increased >4-fold during mitotic arrest compared to interphase, buffering mRNA levels in the absence of new synthesis. Moreover, poly(A) tail-length profiles change during mitotic arrest, strongly suggesting a partial mitotic repression of deadenylation. In contrast, siRNA-directed mRNA degradation machinery remains active. We further show that mitotic mRNA stabilization depends on PABPC1&4. Depletion of PABPC1&4 during mitotic arrest reduces mRNA stability and disrupts the cells' ability to maintain arrest, highlighting the critical physiological role of mitotic transcriptome buffering.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"21 5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0