EMBO ReportsPub Date : 2025-09-01Epub Date: 2025-08-11DOI: 10.1038/s44319-025-00541-2
Na Jiang, Jing Wu, Yating He, Rui Zhang, Mengmeng Ji, Linjing Zhu, Shengwei Cui, Qiao You, Yurong Cai, Bingxin Liu, Ruining Lyu, Yuxin Chen, Jin Zhu, Zhiwei Wu
{"title":"sVEGFR1 up-regulation via EGR1 impairs vascular repair in SFTSV-induced hemorrhage.","authors":"Na Jiang, Jing Wu, Yating He, Rui Zhang, Mengmeng Ji, Linjing Zhu, Shengwei Cui, Qiao You, Yurong Cai, Bingxin Liu, Ruining Lyu, Yuxin Chen, Jin Zhu, Zhiwei Wu","doi":"10.1038/s44319-025-00541-2","DOIUrl":"10.1038/s44319-025-00541-2","url":null,"abstract":"<p><p>Hemorrhage is a major pathological manifestation of certain viral infections, such as severe fever with thrombocytopenia syndrome (SFTS), Ebola, Crimean-Congo hemorrhagic fever and Dengue. SFTS is an emerging viral hemorrhagic fever caused by the SFTS virus (SFTSV). Hemorrhage and angiogenesis dysfunction are key manifestations of SFTSV infection but the underlying mechanisms remain unclear. Here, we demonstrate that SFTSV infection increases soluble vascular endothelial growth factor-receptor 1 (sVEGFR1) secretion from monocytes/macrophages. Increased sVEGFR1 in the serum of SFTS patients is positively correlated with disease severity. Moreover, we show that SFTSV induces sVEGFR1 upregulation via early growth response gene 1 (EGR1), of which VEGFR1 is a downstream target. Serum from SFTS patients containing high levels of sVEGFR1 inhibit angiogenesis, which can be reversed by removal of sVEGFR1. Treatment of SFTSV-infected animals with sVEGFR1 neutralizing antibodies improves angiogenesis and prevents blood vessel leaks in vivo. In conclusion, we show that SFTSV infection induces sVEGFR1 secretion through EGR1 upregulation, thereby contributing to hemorrhage.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4477-4502"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO ReportsPub Date : 2025-09-01Epub Date: 2025-08-26DOI: 10.1038/s44319-025-00560-z
Alexander Sebastian Hauser
{"title":"The future of reviews : Will LLMs render them obsolete?","authors":"Alexander Sebastian Hauser","doi":"10.1038/s44319-025-00560-z","DOIUrl":"10.1038/s44319-025-00560-z","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4397-4401"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO ReportsPub Date : 2025-09-01Epub Date: 2025-08-11DOI: 10.1038/s44319-025-00543-0
Katsufumi Dejima, Keita Yoshida, Shohei Mitani
{"title":"Dual roles of EGO-1 and RRF-1 in regulating germline exo-RNAi efficiency in Caenorhabditis elegans.","authors":"Katsufumi Dejima, Keita Yoshida, Shohei Mitani","doi":"10.1038/s44319-025-00543-0","DOIUrl":"10.1038/s44319-025-00543-0","url":null,"abstract":"<p><p>RNA interference (RNAi) is widely used in life science research and is critical for diverse biological processes, such as germline development and antiviral defense. In the germline of Caenorhabditis elegans, exogenous RNAi (exo-RNAi), the RNA-dependent RNA polymerases EGO-1 and RRF-1 play redundant roles in facilitating small RNA amplification. However, their coordination during the regulation of exo-RNAi processes in the germline remains unclear. Here, we examine non-null mutants of the ego-1 gene and find that ego-1(S1198L) animals exhibit germline exo-RNAi defects with normal fertility, abnormalities in germ granules, and synthetic temperature-dependent sterility with rrf-1. The exo-RNAi defects in ego-1(S1198L) are partially restored by inhibiting hrde-1 and znfx-1. Germline exo-RNAi defects are observed in wild-type and ego-1(S1198L) heterozygous descendants derived from ego-1(S1198L), but these are suppressed by ancestral inhibition of rrf-1. Our data reveal a dual role for EGO-1 in the positive regulation of germline exo-RNAi: it not only mediates target silencing through its RNA-dependent RNA polymerase activity, but also licenses exo-RNAi gene expression, which is antagonized by RRF-1.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4503-4531"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO ReportsPub Date : 2025-09-01DOI: 10.1038/s44319-025-00568-5
Isabell Rosenkranz, Sarah Mermet, Vasiliki Zacharaki, Peter Kindgren
{"title":"Cis- and trans-action of the cold-induced lncRNAs, SVALKA and SVALNA, regulate CBF1 and CBF3 in Arabidopsis.","authors":"Isabell Rosenkranz, Sarah Mermet, Vasiliki Zacharaki, Peter Kindgren","doi":"10.1038/s44319-025-00568-5","DOIUrl":"10.1038/s44319-025-00568-5","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are emerging as key regulatory players of coding gene expression in eukaryotes. Here, we investigate the roles of the lncRNAs SVALKA (SVK) and SVALNA (SVN) in regulating CBF1 and CBF3 gene expression in Arabidopsis under cold stress conditions. We integrated omics approaches, together with genetics and molecular biology, to uncover the transcriptional dynamics and regulatory mechanisms of SVK and SVN. Our results demonstrate that SVK functions as a cis- and trans-acting lncRNA, regulating both CBF1 and CBF3 through RNAPII collision and chromatin remodeling, while SVN serves a cis role by negatively regulating CBF3 via a RNAPII collision mechanism. We identified isoforms of SVK, originating from distinct transcription start sites and undergo alternative splicing which might be important to adapt stability, crucial for the regulatory functions. Furthermore, we show that two positionally conserved lncRNAs, originating from the upstream antisense strand of neighboring genes, can have different molecular mechanisms to regulate their targets. This study elucidates the complex interplay of lncRNAs in gene regulation, highlighting their essential roles in modulating responses to environmental stresses. Our findings contribute to a deeper understanding of the mechanisms underlying lncRNA functionality and their significance in gene regulatory networks in eukaryotes.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A MeA Tac1 neural circuit mediates anxiety-like behaviors in mice.","authors":"Yao Wang, Jiu-Ye Qiao, Mei-Hui Yue, Xin-Yue Lv, Si-Ran Wang, Qian-Qian Yang, Han-Yun Kang, Hua-Li Yu, Xiao-Xiao He, Xiao-Juan Zhu, Zi-Xuan He","doi":"10.1038/s44319-025-00528-z","DOIUrl":"10.1038/s44319-025-00528-z","url":null,"abstract":"<p><p>Anxiety is an emotion characterized by worried thoughts and feelings of unease, often accompanied by physical symptoms such as sweating and dizziness. Unlike other negative emotions, the neural circuits underlying anxiety are not well understood. Here we report that Tachykinin Precursor 1 (Tac1)-expressing neurons in the medial amygdala (MeA) respond to the transition from high anxiety to low anxiety states. The MeATac1 neurons regulate anxiety-like behaviors in mice bidirectionally. We also show that GABAergic neurons in the ventral tegmental area (VTA)<sup>GABA</sup>→MeA<sup>Tac1</sup>→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) circuit contribute to anxiety-like behavior in mice. Our findings reveal a circuit of Tac1 neurons in the MeA that mediates anxiety-like behaviors in mice.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4340-4363"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation.","authors":"Tappei Mishina, Aurélien Courtois, Shuhei Yoshida, Kohei Asai, Hiroshi Kiyonari, Tomoya S Kitajima","doi":"10.1038/s44319-025-00539-w","DOIUrl":"10.1038/s44319-025-00539-w","url":null,"abstract":"<p><p>Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in acentrosomal spindle bipolarization and homologous chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region, where merotelic kinetochore-microtubule attachments are favored to form. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and reveal a spatially differential requirement for homologous chromosome biorientation within the spindle.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4419-4435"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO ReportsPub Date : 2025-09-01Epub Date: 2025-07-23DOI: 10.1038/s44319-025-00520-7
Declan Whyte, Sophie L Fisher, Christopher G J McKenzie, David Sumpton, Sandeep Dhayade, Emmanuel Dornier, Madeleine Moore, David Novo, Jasmine Peters, Robert Wiesheu, Michalis D Gounis, Dale M Watt, John B G Mackey, Amanda J McFarlane, Frédéric Fercoq, Carolina Dehesa Caballero, Keara L Redmond, Louise E Mitchell, Eve Anderson, Gemma Thomson, Ann Hedley, William Clark, Shannen Leroi, Lindsey N Dzierozynski, Juan J Apiz Saab, Caroline A Lewis, Alexander Muir, Christopher J Halbrook, Douglas Strathdee, Rene Jackstadt, Colin Nixon, Philip Dunne, Leo M Carlin, Iain R Macpherson, Edward W Roberts, Seth B Coffelt, Karen Blyth, Owen J Sansom, Jim C Norman, Johan Vande Voorde, Cassie J Clarke
{"title":"Uridine phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes.","authors":"Declan Whyte, Sophie L Fisher, Christopher G J McKenzie, David Sumpton, Sandeep Dhayade, Emmanuel Dornier, Madeleine Moore, David Novo, Jasmine Peters, Robert Wiesheu, Michalis D Gounis, Dale M Watt, John B G Mackey, Amanda J McFarlane, Frédéric Fercoq, Carolina Dehesa Caballero, Keara L Redmond, Louise E Mitchell, Eve Anderson, Gemma Thomson, Ann Hedley, William Clark, Shannen Leroi, Lindsey N Dzierozynski, Juan J Apiz Saab, Caroline A Lewis, Alexander Muir, Christopher J Halbrook, Douglas Strathdee, Rene Jackstadt, Colin Nixon, Philip Dunne, Leo M Carlin, Iain R Macpherson, Edward W Roberts, Seth B Coffelt, Karen Blyth, Owen J Sansom, Jim C Norman, Johan Vande Voorde, Cassie J Clarke","doi":"10.1038/s44319-025-00520-7","DOIUrl":"10.1038/s44319-025-00520-7","url":null,"abstract":"<p><p>Understanding mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches to reduce metastasis. Here we identify uracil as a metastasis-associated metabolite in genetically engineered mouse models of cancer and in patients with metastatic breast cancer. Uracil is generated by the enzyme uridine phosphorylase-1 (UPP1), and we find that neutrophils are a significant source of UPP1 in metastatic cancer. Mammary tumours increase expression of adhesion molecules on the neutrophil surface, in a UPP1-dependent manner, leading to decreased neutrophil motility in the pre-metastatic lung. UPP1-expressing neutrophils suppress T-cell proliferation, and the UPP1 product uracil increases fibronectin deposition in the extracellular microenvironment. Knockout or inhibition of UPP1 in mice with mammary tumours increases T-cell numbers and reduces fibronectin content in the lung, and decreases the proportion of mice that develop lung metastasis. These data indicate that UPP1 influences neutrophil behaviour and extracellular matrix deposition in the lung, and suggest that circulating uracil could be a marker of metastasis, and that pharmacological inhibition of UPP1 could be a strategy to reduce recurrence.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4248-4282"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMBO ReportsPub Date : 2025-09-01Epub Date: 2025-08-18DOI: 10.1038/s44319-025-00545-y
Jordan D Lin, Beth Nicholson, Alexander W Ensminger
{"title":"A bacterial toxin-antitoxin system involved in an unusual response to genotoxic stress.","authors":"Jordan D Lin, Beth Nicholson, Alexander W Ensminger","doi":"10.1038/s44319-025-00545-y","DOIUrl":"10.1038/s44319-025-00545-y","url":null,"abstract":"<p><p>To contend with environmental challenges, bacteria have evolved numerous stress response pathways. A notable example is the adoption of a dormant state called persistence, whereby cells reversibly restrict their growth and await favorable conditions. The genetics of persistence remain poorly understood, and genes called toxin-antitoxin (TA) systems have controversially been implicated in this phenotype. To examine their role in persistence, we construct a pan-TA deletion strain of the bacterial pathogen Legionella pneumophila and test its capacity to survive diverse stresses. We identify a single predicted TA system, GndRX, that under genotoxic stress conditions leads to cell death rather than promoting survival, whereas ∆gndRX cells adopt a viable but nonculturable state. Strikingly, this enhanced survival is conferred to wild-type cells in a contact-dependent manner during co-culture. Despite having homology to other TA systems, GndRX displays non-canonical activity, and we hypothesize that it has undergone functional domestication by the cell. Overall, our work reveals both a new physiological function for TA systems in bacteria as well as a heretofore undescribed phenomenon of contact-dependent survival within persister cells.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4532-4562"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Centrosomal actin pool levels regulated by localized PKA set the threshold for T cell polarization.","authors":"Morgane Simao, Fabienne Régnier, Clotilde Randriamampita","doi":"10.1038/s44319-025-00533-2","DOIUrl":"10.1038/s44319-025-00533-2","url":null,"abstract":"<p><p>T lymphocyte migration triggered by chemokine stimulation is preceded by cell polarization. The acquisition of this asymmetry requires a profound cell rearrangement, particularly of the cytoskeleton. The mechanism by which a uniform signal triggered by chemokine receptors rapidly leads to this asymmetry is largely elusive. Using cell imaging, we emphasize that the centrosome dictates the position of the polarization axis in T lymphocytes. Mechanistically, we highlight that the T cell shape is controlled by the amount of actin filaments surrounding the centrosome. In resting conditions as well as after chemokine stimulation, the activity of a specific pool of protein kinase A regulates this cytoskeleton compartment. Once the centrosomal actin is reduced below a certain threshold, the symmetry breaking is catalyzed. This study points to a critical protein kinase A signaling pathway in the establishment of the immune response.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4436-4455"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}