EMBO Reports最新文献_第2页

The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification. NuRD成分CHD3在颅神经嵴细胞分化过程中促进BMP信号传导。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1038/s44319-025-00555-w

Zoe H Mitchell, Joery den Hoed, Willemijn Claassen, Martina Demurtas, Laura Deelen, Philippe M Campeau, Karen Liu, Simon E Fisher, Marco Trizzino

{"title":"The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification.","authors":"Zoe H Mitchell, Joery den Hoed, Willemijn Claassen, Martina Demurtas, Laura Deelen, Philippe M Campeau, Karen Liu, Simon E Fisher, Marco Trizzino","doi":"10.1038/s44319-025-00555-w","DOIUrl":"10.1038/s44319-025-00555-w","url":null,"abstract":"Pathogenic genetic variants in the NuRD component CHD3 cause Snijders Blok-Campeau Syndrome, a neurodevelopmental disorder manifesting with intellectual disability and craniofacial anomalies. To investigate the role of CHD3 in craniofacial development, we differentiated control and CHD3-depleted human-induced pluripotent stem cells into cranial neural crest cells (CNCCs). In control lines, CHD3 is upregulated in early stages of CNCC specification, where it enhances the BMP signalling response by opening chromatin at BMP-responsive cis-regulatory elements and by increasing expression of BMP-responsive transcription factors, including DLX paralogs. CHD3 loss leads to repression of BMP target genes and loss of chromatin accessibility at cis-regulatory elements usually bound by BMP-responsive factors, causing an imbalance between BMP and Wnt signalling. Consequently, the CNCC specification fails, replaced by aberrant early-mesoderm identity, which can be partially rescued by titrating Wnt levels. Our findings highlight a novel role for CHD3 as a pivotal regulator of BMP signalling, essential for proper neural crest specification and craniofacial development. Moreover, these results suggest a molecular mechanism for the craniofacial anomalies of Snijders Blok-Campeau Syndrome.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4723-4741"},"PeriodicalIF":6.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947122","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}

引用次数: 0

Cargoes move from cis to trans-Golgi compartments and concentrate in the TGN before exiting. 货物从顺式高尔基车厢转移到跨式高尔基车厢，并在出口前集中在TGN。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-10-01 Epub Date: 2025-09-03 DOI: 10.1038/s44319-025-00548-9

Marinella Pirozzi, Ilenia Agliarulo, Rosaria Di Martino, Vincenzo Manuel Marzullo, Micaela Quarto, Gabriele Turacchio, Galina V Beznoussenko, Domenico Russo, Alberto Luini, Alexander A Mironov, Seetharaman Parashuraman

{"title":"Cargoes move from cis to trans-Golgi compartments and concentrate in the TGN before exiting.","authors":"Marinella Pirozzi, Ilenia Agliarulo, Rosaria Di Martino, Vincenzo Manuel Marzullo, Micaela Quarto, Gabriele Turacchio, Galina V Beznoussenko, Domenico Russo, Alberto Luini, Alexander A Mironov, Seetharaman Parashuraman","doi":"10.1038/s44319-025-00548-9","DOIUrl":"10.1038/s44319-025-00548-9","url":null,"abstract":"The classical models of intra-Golgi transport envision a movement of cargoes from cis- to trans-Golgi, followed by their sorting at the trans-Golgi network (TGN). During this vectorial transport, the cargoes are processed by sequentially acting glycosylation enzymes. A number of studies challenged the vectorial transport model and proposed alternative transport routes bypassing either directional transport or the TGN. We have re-visited intra-Golgi transport using varied cargo synchronization protocols, employing both imaging and biochemical methods. We find that cargoes move vectorially across the Golgi stack and reach the TGN. Cell type-dependent variations in transport kinetics and the limited resolution of fluorescence microscopy could have influenced earlier discrepant interpretations. Further, we find that exit from TGN is a rate-limiting step leading to the accumulation of cargoes there before their monoexponential exit. These findings support an intriguing model of intra-Golgi transport, which involves classical vectorial transport across the Golgi stack followed by a non-maturation-based transport from the stack to the TGN.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4742-4765"},"PeriodicalIF":6.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991732","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}

引用次数: 0

RNase III cleavage sites spread across splice junctions enforce sequential snoRNA processing. RNase III切割位点分布在剪接节点上，强制进行顺序的snoRNA加工。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1038/s44319-025-00553-y

Valérie Migeot, Yves Mary, Etienne Fafard-Couture, Pierre Lombard, François Bachand, Michelle S Scott, Carlo Yague-Sanz

{"title":"RNase III cleavage sites spread across splice junctions enforce sequential snoRNA processing.","authors":"Valérie Migeot, Yves Mary, Etienne Fafard-Couture, Pierre Lombard, François Bachand, Michelle S Scott, Carlo Yague-Sanz","doi":"10.1038/s44319-025-00553-y","DOIUrl":"10.1038/s44319-025-00553-y","url":null,"abstract":"Small nucleolar RNAs (snoRNAs) are a class of eukaryotic non-coding RNA molecules whose precursor transcripts are capped and polyadenylated. However, these end modifications are detrimental to snoRNA function and must be removed, a process typically involving excision from introns and/or endonucleolytic cleavage. For RNA precursors that host multiple snoRNAs, the sequence of maturation events is potentially important, but not well understood. Here, we report a new mode of maturation concerning snoRNA pairs that are co-hosted in the intron and the adjacent 3' exon of a precursor transcript. For a snoRNA pair with this arrangement in Schizosaccharomyces pombe, we found that the sequence surrounding an exon-exon junction within their precursor transcript folds into a hairpin after splicing of the intron. This hairpin recruits the RNase III ortholog Pac1, which participates in the maturation of the downstream snoRNA by cleaving the precursor. Our findings suggest that conditional RNase III cleavage signals hidden in an exon-exon junction evolved to enforce sequential snoRNA processing. Sequence analysis suggests that this mechanism is conserved in animals and plants.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4675-4690"},"PeriodicalIF":6.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946983","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}

引用次数: 0

Streptococcus pyogenes EVs induce the alternative inflammasome via caspase-4/-5 in human monocytes. 化脓性链球菌EVs通过caspase-4/-5在人单核细胞中诱导替代炎性体。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-10-01 Epub Date: 2025-09-08 DOI: 10.1038/s44319-025-00558-7

Kathrin Krause, Sandra Franch Arroyo, Matteo Ugolini, Tonya Kueck, Timothy J Sullivan, Eric J C Gálvez, Matthias Muenzner, Christian Goosmann, Volker Brinkmann, Christian K Frese, Kathirvel Alagesan, Tim Vierbuchen, Holger Heine, Ulrike Resch, Leif E Sander, Emmanuelle Charpentier

{"title":"Streptococcus pyogenes EVs induce the alternative inflammasome via caspase-4/-5 in human monocytes.","authors":"Kathrin Krause, Sandra Franch Arroyo, Matteo Ugolini, Tonya Kueck, Timothy J Sullivan, Eric J C Gálvez, Matthias Muenzner, Christian Goosmann, Volker Brinkmann, Christian K Frese, Kathirvel Alagesan, Tim Vierbuchen, Holger Heine, Ulrike Resch, Leif E Sander, Emmanuelle Charpentier","doi":"10.1038/s44319-025-00558-7","DOIUrl":"10.1038/s44319-025-00558-7","url":null,"abstract":"The sensing of Gram-negative Extracellular Vesicles (EVs) by the innate immune system has been extensively studied in the past decade. In contrast, recognition of Gram-positive EVs by innate immune cells remains poorly understood. Comparative genome-wide transcriptional analysis in human monocytes uncovered that S. pyogenes EVs induce proinflammatory signatures that are markedly distinct from those of their parental cells. Among the 209 genes exclusively upregulated by EVs, caspase-5 prompted us to study inflammasome signaling pathways in depth. We show that lipoteichoic acid (LTA), a structural component of Gram-positive bacterial membranes present on EVs from S. pyogenes and other Gram-positive species, is sensed by TLR2 which triggers the alternative inflammasome composed of NLRP3 and the inflammatory caspases-4/-5 to mount an IL-1β response without inducing cell death. For S. pyogenes, we identify TLR8 as a sensor to mediate caspase-4/-5-dependent IL-1β secretion. Notably, inflammasome activation by intact bacteria is independent of the global virulence regulator CovS in monocytes. Overall, our study highlights a new role for TLR2 and caspase-4/-5 in the recognition of Gram-positive EVs in human monocytes.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4847-4885"},"PeriodicalIF":6.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029186","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}

引用次数: 0

E69K mutation in β-tubulin 2 blocks cell wall integrity signaling during plant cell elongation. β-微管蛋白2 E69K突变阻断植物细胞伸长过程中细胞壁完整性信号传导。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-09-30 DOI: 10.1038/s44319-025-00507-4

Huanhuan Yang, Jie Wang, Guangda Wang, Chaofeng Wang, Xiaxia Zhang, Juan Tian, Yanjun Yu, Zhaosheng Kong

{"title":"E69K mutation in β-tubulin 2 blocks cell wall integrity signaling during plant cell elongation.","authors":"Huanhuan Yang, Jie Wang, Guangda Wang, Chaofeng Wang, Xiaxia Zhang, Juan Tian, Yanjun Yu, Zhaosheng Kong","doi":"10.1038/s44319-025-00507-4","DOIUrl":"https://doi.org/10.1038/s44319-025-00507-4","url":null,"abstract":"The intact cell wall is the prerequisite for plant cell morphogenesis. Loss of function in FRA1/KINESIN-4A, which encodes a microtubule-based kinesin motor, causes dwarfed growth phenotypes with reduced cell wall mechanics. However, the underlying mechanisms remain elusive. Here, using genetic screening, we identify a suppressor of fra1 (sofa1) mutation that specifically suppresses the dwarf phenotype of the fra1 mutant. The sofa1 carries an E69K mutation in β-Tubulin 2 (TUB2), and the dominant suppressive effect of E69K mutation is conserved among β-tubulins. We further reveal that incorporation of TUB2E69K affects microtubule stability, yet fails to rescue the cell wall defects or lateral displacement of microtubules in fra1. Combining with transcriptomic analysis, we propose that the E69K mutation of TUB2 potentially restores the cell elongation by blocking the cell wall integrity (CWI) signaling. Our study sheds new light on the complex mechanism underlying the dwarfism of the fra1 mutant, and further proposes a potential model by which microtubules control plant cell elongation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198808","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

Scientists targeted by dark PR tactics : Several academic scientists critical of de-extinction projects have become the targets of anonymous smear articles and weaponized copyright infringement claims. 科学家成为黑暗公关策略的目标：一些批评灭绝项目的学术科学家已经成为匿名诽谤文章的目标，并成为侵犯版权索赔的武器。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-09-29 DOI: 10.1038/s44319-025-00579-2

Howard Wolinsky, Holger Breithaupt, Yehu Moran

引用次数: 0

For the love of frontier research, or why Elon's rockets keep blowing up. 因为对前沿研究的热爱，或者为什么埃隆的火箭总是爆炸。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-09-29 DOI: 10.1038/s44319-025-00587-2

Nektarios Tavernarakis

引用次数: 0

The deubiquitinase USP17LA negatively regulates T-cell activation and attenuates anti-tumor immunity. 去泛素酶USP17LA负调控t细胞活化并减弱抗肿瘤免疫。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-09-29 DOI: 10.1038/s44319-025-00584-5

Huiling Zhang, Zhihan Guo, Gaigai Wei, Jingjing Yi, Zixi Wang, Yuqi Zhang, Haiping Zhao, Tingrong Ren, Yihan Wang, Jiating Kuang, Zhaoying Sheng, Duanwu Zhang

{"title":"The deubiquitinase USP17LA negatively regulates T-cell activation and attenuates anti-tumor immunity.","authors":"Huiling Zhang, Zhihan Guo, Gaigai Wei, Jingjing Yi, Zixi Wang, Yuqi Zhang, Haiping Zhao, Tingrong Ren, Yihan Wang, Jiating Kuang, Zhaoying Sheng, Duanwu Zhang","doi":"10.1038/s44319-025-00584-5","DOIUrl":"https://doi.org/10.1038/s44319-025-00584-5","url":null,"abstract":"T-cell activation is essential for effective immune responses, yet its precise regulatory mechanisms remain incompletely understood. In this study, we show that the deubiquitinases of the Ubiquitin-Specific Peptidase 17-like (USP17L) family are significantly upregulated following T-cell stimulation. Using CRISPR-mediated gene knockout mice, we demonstrate that USP17LA, but not USP17LB, acts as a negative regulator of T-cell activation. Loss of Usp17la leads to increased production of pro-inflammatory cytokines, enhanced T-cell proliferation and effector functions, without affecting T-cell development or homeostasis. Furthermore, Usp17la deletion augments TCR signaling and anti-tumor immunity, improving T-cell-mediated tumor surveillance in murine tumor models. Mechanistically, proteomic analysis revealed that USP17LA strongly associates with cadherin-binding and calmodulin-binding pathways. Notably, USP17LA interacts with RACK1 and prevents its ubiquitin-dependent degradation, thereby promoting RACK1-mediated suppression of NFAT activity and the subsequent inhibition of T-cell function. These findings establish USP17LA as a pivotal modulator of T-cell activation and suggest that targeting USP17LA could enhance anti-tumor immunity, offering a potential strategy for cancer immunotherapy.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190952","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

The complicated art of writing the perfect CV. 撰写完美简历的复杂艺术。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-09-26 DOI: 10.1038/s44319-025-00586-3

David R Smith

引用次数: 0

Progressive chromosome shape changes during cell divisions. 在细胞分裂过程中，渐进式染色体形状改变。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-09-23 DOI: 10.1038/s44319-025-00577-4

Yasutaka Kakui, Yoshiharu Kusano, Tereza Clarence, Maya Lopez, Todd Fallesen, Toru Hirota, Bhavin S Khatri, Frank Uhlmann

{"title":"Progressive chromosome shape changes during cell divisions.","authors":"Yasutaka Kakui, Yoshiharu Kusano, Tereza Clarence, Maya Lopez, Todd Fallesen, Toru Hirota, Bhavin S Khatri, Frank Uhlmann","doi":"10.1038/s44319-025-00577-4","DOIUrl":"https://doi.org/10.1038/s44319-025-00577-4","url":null,"abstract":"Mitotic chromosomes give genome portions the required compaction and mechanical stability for faithful inheritance during cell divisions. They are shaped by the chromosomal condensin complex. Here, we record human chromosome dimensions from their appearance in prophase over successive times in a mitotic arrest. Chromosomes first appear long and uniformly thin. Then, individual chromosome arms become discernible, which continuously shorten and thicken-the longer a chromosome arm, the thicker it becomes. In the search for a molecular explanation of this behavior, given uniform condensin density, the popular loop extrusion model provides no obvious means by which longer chromosome arms become thicker. Instead, we find that simulations of an alternative loop capture model recapitulate key features of our observations, with re-arranging chromatin rosettes underpinning the gradually developing arm length-to-width relationship. Our analyses portray chromosomes as out-of-equilibrium structures in the process of transitioning towards, but on biologically relevant time scales not typically reaching, steady state.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130275","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