EMBO Reports最新文献_第2页

Regulated localization of transposable element RNA during influenza A virus infection. 甲型流感病毒感染期间转座因子RNA的调控定位。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-16 DOI: 10.1038/s44319-025-00498-2

Marie Lork, Liam Childs, Gauthier Lieber, Florence Kwaschik, Renate König, Benjamin G Hale

{"title":"Regulated localization of transposable element RNA during influenza A virus infection.","authors":"Marie Lork, Liam Childs, Gauthier Lieber, Florence Kwaschik, Renate König, Benjamin G Hale","doi":"10.1038/s44319-025-00498-2","DOIUrl":"https://doi.org/10.1038/s44319-025-00498-2","url":null,"abstract":"Influenza A virus (IAV) infection triggers derepression of host transposable elements (TEs), which have the potential to form double-stranded (ds)RNAs and could enhance innate antiviral immunity. However, the contribution of TEs to stimulating such pathways during infection is unknown, and it remains unclear whether derepressed TEs actually form dsRNAs. Here, we perform strand-specific total RNA-Seq on nucleus-associated and cytosolic fractions from cells infected with wild-type IAV or an engineered IAV lacking NS1, a dsRNA-binding interferon-antagonist protein. Both infections globally increase levels of host TE RNAs with bioinformatic and experimental evidence for double-strandedness. However, NS1-deficient IAV leads to significantly more of these putative dsRNA-forming TEs accumulating in the cytosolic fraction. Co-precipitations identify that wild-type NS1, but not a dsRNA-binding mutant, associates with these TEs, and microscopy shows co-localization of wild-type NS1 with dsRNA in perinuclear regions. Our data reveal the double-stranded nature of some IAV-triggered host TEs and suggest that NS1-mediated sequestration could limit their engagement of cytosolic innate immune sensors.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309715","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}

引用次数: 0

ATR promotes mTORC1 activity via de novo cholesterol synthesis. ATR通过从头胆固醇合成促进mTORC1活性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-13 DOI: 10.1038/s44319-025-00451-3

Naveen Kumar Tangudu, Alexandra N Grumet, Richard Fang, Raquel Buj, Aidan R Cole, Apoorva Uboveja, Amandine Amalric, Baixue Yang, Zhentai Huang, Cassandra Happe, Mai Sun, Stacy L Gelhaus, Matthew L MacDonald, Nadine Hempel, Nathaniel W Snyder, Katarzyna M Kedziora, Alexander J Valvezan, Katherine M Aird

{"title":"ATR promotes mTORC1 activity via de novo cholesterol synthesis.","authors":"Naveen Kumar Tangudu, Alexandra N Grumet, Richard Fang, Raquel Buj, Aidan R Cole, Apoorva Uboveja, Amandine Amalric, Baixue Yang, Zhentai Huang, Cassandra Happe, Mai Sun, Stacy L Gelhaus, Matthew L MacDonald, Nadine Hempel, Nathaniel W Snyder, Katarzyna M Kedziora, Alexander J Valvezan, Katherine M Aird","doi":"10.1038/s44319-025-00451-3","DOIUrl":"10.1038/s44319-025-00451-3","url":null,"abstract":"DNA damage and cellular metabolism exhibit a complex interplay characterized by bidirectional feedback. Key mediators of these pathways include ATR and mTORC1, respectively. Previous studies established ATR as a regulatory upstream factor of mTORC1 during replication stress; however, the precise mechanisms remain poorly defined. Additionally, the activity of this signaling axis in unperturbed cells has not been extensively investigated. We demonstrate that ATR promotes mTORC1 activity across various human cancer cells and both human and mouse normal cells under basal conditions. This effect is enhanced in human cancer cells (SKMEL28, RPMI-7951, HeLa) following knockdown of p16, a cell cycle inhibitor that we have previously found increases mTORC1 activity and here found increases ATR activity. Mechanistically, ATR promotes de novo cholesterol synthesis and mTORC1 activation through the phosphorylation and upregulation of lanosterol synthase (LSS), independently of both CHK1 and the TSC complex. Interestingly, this pathway is distinct from the regulation of mTORC1 by ATM and may be specific to cancer cells. Finally, ATR-mediated increased cholesterol correlates with enhanced localization of mTOR to lysosomes. Collectively, our findings demonstrate a novel connection linking ATR and mTORC1 signaling through the modulation of cholesterol metabolism.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293546","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}

引用次数: 0

Monitoring technology for pest-plant interactions : The need for transdisciplinary research design. 害虫与植物相互作用的监测技术：跨学科研究设计的需要。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-11 DOI: 10.1038/s44319-025-00489-3

Emma Cavazzoni, Sabina Leonelli, Daniele Giannetti, Niccolò Patelli, Giacomo Vaccari, Lara Maistrello, Maria Cristina Pinotti

引用次数: 0

AML patient blasts exhibit polarization defects upon interaction with bone marrow stromal cells. AML患者原细胞在与骨髓基质细胞相互作用时表现出极化缺陷。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-11 DOI: 10.1038/s44319-025-00466-w

Khansa Saadallah, Benoît Vianay, Louise Bonnemay, Hélène Pasquer, Lois Kelly, Stéphanie Mathis, Cécile Culeux, Raphael Marie, Paul Arthur Meslin, Sofiane Fodil, Paul Chaintreuil, Emeline Kerreneur, Arnaud Jacquel, Emmanuel Raffoux, Rémy Nizard, Camille Lobry, Laurent Blanchoin, Lina Benajiba, Manuel Théry

{"title":"AML patient blasts exhibit polarization defects upon interaction with bone marrow stromal cells.","authors":"Khansa Saadallah, Benoît Vianay, Louise Bonnemay, Hélène Pasquer, Lois Kelly, Stéphanie Mathis, Cécile Culeux, Raphael Marie, Paul Arthur Meslin, Sofiane Fodil, Paul Chaintreuil, Emeline Kerreneur, Arnaud Jacquel, Emmanuel Raffoux, Rémy Nizard, Camille Lobry, Laurent Blanchoin, Lina Benajiba, Manuel Théry","doi":"10.1038/s44319-025-00466-w","DOIUrl":"https://doi.org/10.1038/s44319-025-00466-w","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) polarize in contact with the bone marrow stromal cells constituting their niche. Given the role of cell polarity in protection against tumorigenesis and the importance of the niche in the progression of acute myeloid leukemias (AMLs), we investigated the polarization capacities of leukemic blasts. Using engineered micro-niches and centrosome position with respect to the contact site with stromal cells as a proxy for cell polarization, we show that AML cell lines and primary cells from AML patient blasts are unable to polarize in contact with healthy stromal cells. Exposure to AML patient-derived stromal cells compromises the polarization of healthy adult HSPCs and AML blasts from patients. When cultured in \"bone-marrow-on-a-chip\", stromal cells from a leukemic niche stimulate the migration of healthy HSPCs and AML blast. These results reveal the detrimental influences of both intrinsic transformation and extrinsic contact with transformed stromal cells on the polarization of AML blasts.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274433","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}

引用次数: 0

RNF20-mediated H2B monoubiquitination protects stalled forks from degradation and promotes fork restart. rnf20介导的H2B单泛素化保护停滞分叉免受降解并促进分叉重启。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-10 DOI: 10.1038/s44319-025-00497-3

Debanjali Bhattacharya, Harsh Kumar Dwivedi, Ganesh Nagaraju

引用次数: 0

CD206+ macrophages facilitate wound healing through interactions with Gpnmb^hi fibroblasts. CD206+巨噬细胞通过与Gpnmbhi成纤维细胞相互作用促进伤口愈合。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-10 DOI: 10.1038/s44319-025-00496-4

Azusa Honda, Hiroyuki Koike, Teruyuki Dohi, Eri Toyohara, Sumio Hayakawa, Kazuyuki Tobe, Ichiro Manabe, Rei Ogawa, Yumiko Oishi

{"title":"CD206+ macrophages facilitate wound healing through interactions with Gpnmbhi fibroblasts.","authors":"Azusa Honda, Hiroyuki Koike, Teruyuki Dohi, Eri Toyohara, Sumio Hayakawa, Kazuyuki Tobe, Ichiro Manabe, Rei Ogawa, Yumiko Oishi","doi":"10.1038/s44319-025-00496-4","DOIUrl":"https://doi.org/10.1038/s44319-025-00496-4","url":null,"abstract":"Wound healing is a multifaceted and dynamic sequence of tissue repair and regeneration processes involving interrelated stages: inflammation, regeneration, and remodeling. Throughout these processes, macrophages change their phenotypes and interact with cells and extracellular components to facilitate healing. In particular, macrophages expressing the surface marker CD206 associate with inflammation resolution and tissue repair. However, how CD206+ macrophages contribute to these processes is insufficiently understood. Here, using a mouse model of CD206+ macrophage depletion and single-cell transcriptomics, we report that selective depletion of CD206+ macrophages results in modest but significant delays in wound healing, prolongs inflammation, and significantly reduces the number of Gpnmbhi fibroblasts in injured skin. Single-cell data suggest that CD206+ macrophages communicate with Gpnmbhi fibroblasts via multiple pathways. Notably, topical administration of PDGF-AA to wounds of CD206+ macrophage-depleted mice restores healing processes, identifying PDGF-A signaling from CD206+ macrophages to PDGFRA on fibroblasts as an important mechanism promoting wound healing. Collectively, these data demonstrate that CD206+ macrophages communicate with Gpnmbhi fibroblasts to activate their proliferation and extracellular matrix deposition in wound healing.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265716","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}

引用次数: 0

An alternative mechanism by which If1 prevents ATP hydrolysis by the ATP synthase subcomplex in S. cerevisiae. 在酿酒酵母中If1阻止ATP合成酶亚复合物水解的另一种机制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-09 DOI: 10.1038/s44319-025-00430-8

Orane Lerouley, Isabelle Larrieu, Tom Louis Ducrocq, Benoît Pinson, Marie-France Giraud, Arnaud Mourier

{"title":"An alternative mechanism by which If1 prevents ATP hydrolysis by the ATP synthase subcomplex in S. cerevisiae.","authors":"Orane Lerouley, Isabelle Larrieu, Tom Louis Ducrocq, Benoît Pinson, Marie-France Giraud, Arnaud Mourier","doi":"10.1038/s44319-025-00430-8","DOIUrl":"https://doi.org/10.1038/s44319-025-00430-8","url":null,"abstract":"The mitochondrial F1F0-ATP synthase is crucial for maintaining the ATP/ADP balance which is critical for cell metabolism, ion homeostasis and cell proliferation. This enzyme, conserved across evolution, is found in the mitochondria or chloroplasts of eukaryotic cells and the plasma membrane of bacteria. In vitro studies have shown that the mitochondrial F1F0-ATP synthase is reversible, capable of hydrolyzing instead of synthesizing ATP. In vivo, its reversibility is inhibited by the endogenous peptide If1 (Inhibitory Factor 1), which specifically prevents ATP hydrolysis in a pH-dependent manner. Despite its presumed importance, the loss of If1 in various model organisms does not cause severe phenotypes, suggesting its role may be confined to specific stress or metabolic conditions yet to be discovered. Our analyses indicate that inhibitory peptides are crucial in mitigating mitochondrial depolarizing stress under glyco-oxidative metabolic conditions. Additionally, we found that the absence of If1 destabilizes the nuclear-encoded free F1 subcomplex. This mechanism highlights the role of If1 in preventing harmful ATP wastage, offering new insights into its function under physiological and pathological conditions.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257582","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}

引用次数: 0

Regulated microexon alternative splicing in single neurons tunes synaptic function. 单个神经元微外显子选择性剪接调节突触功能。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-09 DOI: 10.1038/s44319-025-00493-7

Bikash Choudhary, Rebekah Napier-Jameson, Adam Norris

{"title":"Regulated microexon alternative splicing in single neurons tunes synaptic function.","authors":"Bikash Choudhary, Rebekah Napier-Jameson, Adam Norris","doi":"10.1038/s44319-025-00493-7","DOIUrl":"https://doi.org/10.1038/s44319-025-00493-7","url":null,"abstract":"Microexons are important components of the neuronal transcriptome. Though tiny, their splicing is essential for neuronal development and function. Microexons are typically included in the nervous system and skipped in other tissues, but less is known about whether they are alternatively spliced across neuron types, and if so what the regulatory mechanisms and functional consequences might be. We set out to globally address this question in C. elegans using deep single-cell transcriptomes and in vivo splicing reporters. We find widespread alternative microexon splicing across neuron types. Focusing on a broadly-conserved 9-nucleotide exon in the synaptic vesicle gene unc-13, we find that it is completely skipped in olfactory neurons, but completely included in motor neurons. This splicing pattern is established by two neuronal RNA binding proteins which recruit spliceosomal component PRP-40 to mediate microexon inclusion. Cell-specific microexon alternative splicing is functionally important, as forcing microexon inclusion causes olfactory defects, while forcing microexon skipping causes locomotory defects. These locomotory defects are caused by decreased inhibitory motor neuron synaptic transmission and altered synaptic vesicle distribution. Regulatory features of unc-13 microexon splicing are broadly conserved: related MUN-domain genes in worms, flies, and mice invariably encode microexons, and those we tested are subject to similar regulatory principles (e.g. included in motor neurons, skipped in olfactory neurons, and regulated by the same two RNA binding proteins). Thus, not only is microexon inclusion important for nervous system function, but microexon alternative splicing across neurons is important for tuning neuronal function in individual cell types.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257583","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}

引用次数: 0

Meating the moment : Challenges and opportunities for cellular agriculture to produce the foods of the future. 把握当下：细胞农业生产未来食物的挑战与机遇。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-06 DOI: 10.1038/s44319-025-00492-8

Matthew J McNulty, Andrew J Stout, David L Kaplan

引用次数: 0

Retraction Note: Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation. 备注：髓源性生长因子（MYDGF）通过抑制破骨细胞生成和促进成骨细胞分化来保护骨量。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-06-06 DOI: 10.1038/s44319-025-00479-5

Xiaoli Xu, Yixiang Li, Lingfeng Shi, Kaiyue He, Ying Sun, Yan Ding, Biying Meng, Jiajia Zhang, Lin Xiang, Jing Dong, Min Liu, Junxia Zhang, Lingwei Xiang, Guangda Xiang

引用次数: 0