EMBO Reports最新文献_第2页

NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch. NS2 可诱导甲型流感 RNA 聚合酶六聚体，并充当转录到复制的开关。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-07-18 DOI: 10.1038/s44319-024-00208-4

Junqing Sun, Lu Kuai, Lei Zhang, Yufeng Xie, Yanfang Zhang, Yan Li, Qi Peng, Yuekun Shao, Qiuxian Yang, Wen-Xia Tian, Junhao Zhu, Jianxun Qi, Yi Shi, Tao Deng, George F Gao

{"title":"NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch.","authors":"Junqing Sun, Lu Kuai, Lei Zhang, Yufeng Xie, Yanfang Zhang, Yan Li, Qi Peng, Yuekun Shao, Qiuxian Yang, Wen-Xia Tian, Junhao Zhu, Jianxun Qi, Yi Shi, Tao Deng, George F Gao","doi":"10.1038/s44319-024-00208-4","DOIUrl":"10.1038/s44319-024-00208-4","url":null,"abstract":"Genome transcription and replication of influenza A virus (FluA), catalyzed by viral RNA polymerase (FluAPol), are delicately controlled across the virus life cycle. A switch from transcription to replication occurring at later stage of an infection is critical for progeny virion production and viral non-structural protein NS2 has been implicated in regulating the switch. However, the underlying regulatory mechanisms and the structure of NS2 remained elusive for years. Here, we determine the cryo-EM structure of the FluAPol-NS2 complex at ~3.0 Å resolution. Surprisingly, three domain-swapped NS2 dimers arrange three symmetrical FluPol dimers into a highly ordered barrel-like hexamer. Further structural and functional analyses demonstrate that NS2 binding not only hampers the interaction between FluAPol and the Pol II CTD because of steric conflicts, but also impairs FluAPol transcriptase activity by stalling it in the replicase conformation. Moreover, this is the first visualization of the full-length NS2 structure. Our findings uncover key molecular mechanisms of the FluA transcription-replication switch and have implications for the development of antivirals.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723244","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

SOX10 mediates glioblastoma cell-state plasticity. SOX10介导胶质母细胞瘤细胞状态的可塑性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI: 10.1038/s44319-024-00258-8

Ka-Hou Man, Yonghe Wu, Zhenjiang Gao, Anna-Sophie Spreng, Johanna Keding, Jasmin Mangei, Pavle Boskovic, Jan-Philipp Mallm, Hai-Kun Liu, Charles D Imbusch, Peter Lichter, Bernhard Radlwimmer

{"title":"SOX10 mediates glioblastoma cell-state plasticity.","authors":"Ka-Hou Man, Yonghe Wu, Zhenjiang Gao, Anna-Sophie Spreng, Johanna Keding, Jasmin Mangei, Pavle Boskovic, Jan-Philipp Mallm, Hai-Kun Liu, Charles D Imbusch, Peter Lichter, Bernhard Radlwimmer","doi":"10.1038/s44319-024-00258-8","DOIUrl":"10.1038/s44319-024-00258-8","url":null,"abstract":"Phenotypic plasticity is a cause of glioblastoma therapy failure. We previously showed that suppressing the oligodendrocyte-lineage regulator SOX10 promotes glioblastoma progression. Here, we analyze SOX10-mediated phenotypic plasticity and exploit it for glioblastoma therapy design. We show that low SOX10 expression is linked to neural stem-cell (NSC)-like glioblastoma cell states and is a consequence of temozolomide treatment in animal and cell line models. Single-cell transcriptome profiling of Sox10-KD tumors indicates that Sox10 suppression is sufficient to induce tumor progression to an aggressive NSC/developmental-like phenotype, including a quiescent NSC-like cell population. The quiescent NSC state is induced by temozolomide and Sox10-KD and reduced by Notch pathway inhibition in cell line models. Combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice carrying Sox10-KD tumors, validating our experimental therapy approach. In summary, SOX10 suppression mediates glioblastoma progression through NSC/developmental cell-state transition, including the induction of a targetable quiescent NSC state. This work provides a rationale for the design of tumor therapies based on single-cell phenotypic plasticity analysis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282183","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

Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity. 天冬氨酰蛋白酶以宿主肌动蛋白核聚体蛋白为靶标，限制上皮细胞的先天性免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI: 10.1038/s44319-024-00270-y

Sandip Patra, Rupinder Kaur

{"title":"Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity.","authors":"Sandip Patra, Rupinder Kaur","doi":"10.1038/s44319-024-00270-y","DOIUrl":"10.1038/s44319-024-00270-y","url":null,"abstract":"Epithelial-immune cell communication is pivotal to control microbial infections. We show that glycosylphosphatidylinositol-linked aspartyl proteases (Yapsins) of the human opportunistic pathogenic yeast Candida glabrata (Cg) thwart epithelial cell (EC)-neutrophil signalling by targeting the EC protein, Arpc1B (actin nucleator Arp2/3 complex subunit), which leads to actin disassembly and impeded IL-8 secretion by ECs. Further, the diminished IL-8 secretion inhibits neutrophil migration, and protects Cg from the neutrophil-mediated killing. CgYapsin-dependent Arpc1B degradation requires Arginine-142 in Arpc1B, and leads to reduced Arpc1B-p38 MAPK interaction and downregulated p38 signalling. Consistently, Arpc1B or p38 deletion promotes survival of the Cg aspartyl protease-deficient mutant in ECs. Importantly, kidneys of the protease-deficient mutant-infected mice display elevated immune cell infiltration and cytokine secretion, implicating CgYapsins in immune response suppression in vivo. Besides delineating Cg-EC interplay, our results uncover a novel target, Arpc1B, that pathogens attack to constrain the host signalling networks, and link Arpc1B mechanistically with p38 activation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343797","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

Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2'O-methylation. TLR8 对细菌 RNA 的感应需要 RNase 6 处理，并受到 RNA 2'O- 甲基化的抑制。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1038/s44319-024-00281-9

Ivanéia V Nunes, Luisa Breitenbach, Sarah Pawusch, Tatjana Eigenbrod, Swetha Ananth, Paulina Schad, Oliver T Fackler, Falk Butter, Alexander H Dalpke, Lan-Sun Chen

{"title":"Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2'O-methylation.","authors":"Ivanéia V Nunes, Luisa Breitenbach, Sarah Pawusch, Tatjana Eigenbrod, Swetha Ananth, Paulina Schad, Oliver T Fackler, Falk Butter, Alexander H Dalpke, Lan-Sun Chen","doi":"10.1038/s44319-024-00281-9","DOIUrl":"10.1038/s44319-024-00281-9","url":null,"abstract":"TLR8 senses single-stranded RNA (ssRNA) fragments, processed via cleavage by ribonuclease (RNase) T2 and RNase A family members. Processing by these RNases releases uridines and purine-terminated residues resulting in TLR8 activation. Monocytes show high expression of RNase 6, yet this RNase has not been analyzed for its physiological contribution to the recognition of bacterial RNA by TLR8. Here, we show a role for RNase 6 in TLR8 activation. BLaER1 cells, transdifferentiated into monocyte-like cells, as well as primary monocytes deficient for RNASE6 show a dampened TLR8-dependent response upon stimulation with isolated bacterial RNA (bRNA) and also upon infection with live bacteria. Pretreatment of bacterial RNA with recombinant RNase 6 generates fragments that induce TLR8 stimulation in RNase 6 knockout cells. 2'O-RNA methyl modification, when introduced at the first uridine in the UA dinucleotide, impairs processing by RNase 6 and dampens TLR8 stimulation. In summary, our data show that RNase 6 processes bacterial RNA and generates uridine-terminated breakdown products that activate TLR8.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371326","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

Author Correction: LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis. 作者更正：LncRNA-PAGBC 作为 microRNA 海绵促进胆囊肿瘤发生

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 DOI: 10.1038/s44319-024-00185-8

Xiang-Song Wu, Fang Wang, Huai-Feng Li, Yun-Ping Hu, Lin Jiang, Fei Zhang, Mao-Lan Li, Xu-An Wang, Yun-Peng Jin, Yi-Jian Zhang, Wei Lu, Wen-Guang Wu, Yi-Jun Shu, Hao Weng, Yang Cao, Run-Fa Bao, Hai-Bin Liang, Zheng Wang, Yi-Chi Zhang, Wei Gong, Lei Zheng, Shu-Han Sun, Ying-Bin Liu

引用次数: 0

Circadian rhythms of macrophages are altered by the acidic tumor microenvironment. 酸性肿瘤微环境改变了巨噬细胞的昼夜节律。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1038/s44319-024-00288-2

Amelia M Knudsen-Clark, Daniel Mwangi, Juliana Cazarin, Kristina Morris, Cameron Baker, Lauren M Hablitz, Matthew N McCall, Minsoo Kim, Brian J Altman

{"title":"Circadian rhythms of macrophages are altered by the acidic tumor microenvironment.","authors":"Amelia M Knudsen-Clark, Daniel Mwangi, Juliana Cazarin, Kristina Morris, Cameron Baker, Lauren M Hablitz, Matthew N McCall, Minsoo Kim, Brian J Altman","doi":"10.1038/s44319-024-00288-2","DOIUrl":"10.1038/s44319-024-00288-2","url":null,"abstract":"Tumor-associated macrophages (TAMs) are prime therapeutic targets due to their pro-tumorigenic functions, but varying efficacy of macrophage-targeting therapies highlights our incomplete understanding of how macrophages are regulated within the tumor microenvironment (TME). The circadian clock is a key regulator of macrophage function, but how circadian rhythms of macrophages are influenced by the TME remains unknown. Here, we show that conditions associated with the TME such as polarizing stimuli, acidic pH, and lactate can alter circadian rhythms in macrophages. While cyclic AMP (cAMP) has been reported to play a role in macrophage response to acidic pH, our results indicate pH-driven changes in circadian rhythms are not mediated solely by cAMP signaling. Remarkably, circadian disorder of TAMs was revealed by clock correlation distance analysis. Our data suggest that heterogeneity in circadian rhythms within the TAM population level may underlie this circadian disorder. Finally, we report that circadian regulation of macrophages suppresses tumor growth in a murine model of pancreatic cancer. Our work demonstrates a novel mechanism by which the TME influences macrophage biology through modulation of circadian rhythms.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460722","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

Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes. Ehbp1 可将 Wnt/Wingless 有序地分拣到基底侧和顶端细胞膜。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1038/s44319-024-00289-1

Yuan Gao, Jing Feng, Yansong Zhang, Mengyuan Yi, Lebing Zhang, Yan Yan, Alan Jian Zhu, Min Liu

{"title":"Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes.","authors":"Yuan Gao, Jing Feng, Yansong Zhang, Mengyuan Yi, Lebing Zhang, Yan Yan, Alan Jian Zhu, Min Liu","doi":"10.1038/s44319-024-00289-1","DOIUrl":"10.1038/s44319-024-00289-1","url":null,"abstract":"Wingless (Wg)/Wnt signaling plays a critical role in both development and adult tissue homeostasis. In the Drosophila larval wing disc epithelium, the orderly delivery of Wg/Wnt to the apical and basal cell surfaces is essential for wing development. Here, we identified Ehbp1 as the switch that dictates the direction of Wg/Wnt polarized intracellular transport: the Adaptor Protein complex 1 (AP-1) delivers Wg/Wnt to the basolateral cell surface, and its sequestration by Ehbp1 redirects Wg/Wnt for apical delivery. Genetic analyses showed that Ehbp1 specifically regulates the polarized distribution of Wg/Wnt, a process that depends on the dedicated Wg/Wnt cargo receptor Wntless. Mechanistically, Ehbp1 competes with Wntless for AP-1 binding, thereby preventing the unregulated basolateral Wg/Wnt transport. Reducing Ehbp1 expression, or removing the coiled-coil motifs within its bMERB domain, leads to basolateral Wg/Wnt accumulation. Importantly, the regulation of polarized Wnt delivery by EHBP1 is conserved in vertebrates. The generality of this switch mechanism for regulating intracellular transport remains to be determined in future studies.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460723","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

Abundant mRNA m¹A modification in dinoflagellates: a new layer of gene regulation. 甲藻中丰富的 mRNA m1A 修饰：基因调控的新层次。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-02 DOI: 10.1038/s44319-024-00234-2

Chongping Li, Ying Li, Jia Guo, Yuci Wang, Xiaoyan Shi, Yangyi Zhang, Nan Liang, Honghui Ma, Jie Yuan, Jiawei Xu, Hao Chen

{"title":"Abundant mRNA m1A modification in dinoflagellates: a new layer of gene regulation.","authors":"Chongping Li, Ying Li, Jia Guo, Yuci Wang, Xiaoyan Shi, Yangyi Zhang, Nan Liang, Honghui Ma, Jie Yuan, Jiawei Xu, Hao Chen","doi":"10.1038/s44319-024-00234-2","DOIUrl":"10.1038/s44319-024-00234-2","url":null,"abstract":"Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119264","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

Robust tissue pattern formation by coupling morphogen signal and cell adhesion. 通过形态发生信号与细胞粘附的耦合，形成稳健的组织模式。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-09-27 DOI: 10.1038/s44319-024-00261-z

Kosuke Mizuno, Tsuyoshi Hirashima, Satoshi Toda

{"title":"Robust tissue pattern formation by coupling morphogen signal and cell adhesion.","authors":"Kosuke Mizuno, Tsuyoshi Hirashima, Satoshi Toda","doi":"10.1038/s44319-024-00261-z","DOIUrl":"10.1038/s44319-024-00261-z","url":null,"abstract":"Morphogens, locally produced signaling molecules, form a concentration gradient to guide tissue patterning. Tissue patterns emerge as a collaboration between morphogen diffusion and responsive cell behaviors, but the mechanisms through which diffusing morphogens define precise spatial patterns amidst biological fluctuations remain unclear. To investigate how cells respond to diffusing proteins to generate tissue patterns, we develop SYMPLE3D, a 3D culture platform. By engineering gene expression responsive to artificial morphogens, we observe that coupling morphogen signals with cadherin-based adhesion is sufficient to convert a morphogen gradient into distinct tissue domains. Morphogen-induced cadherins gather activated cells into a single domain, removing ectopically activated cells. In addition, we reveal a switch-like induction of cadherin-mediated compaction and cell mixing, homogenizing activated cells within the morphogen gradient to form a uniformly activated domain with a sharp boundary. These findings highlight the cooperation between morphogen gradients and cell adhesion in robust tissue patterning and introduce a novel method for tissue engineering to develop new tissue domains in organoids.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343800","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

Publisher Correction: Emerging toolkits for decoding the co-occurrence of modified histones and chromatin proteins. 出版商更正：解码修饰组蛋白和染色质蛋白共存的新兴工具包。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-11-01 DOI: 10.1038/s44319-024-00269-5

Anne-Sophie Pepin, Robert Schneider

引用次数: 0