Cell最新文献 - Book学术

Structural basis for the concurrence of template recycling and RNA capping in SARS-CoV-2.

IF 42.5 1区生物学

Cell Pub Date : 2025-10-22 DOI: 10.1016/j.cell.2025.09.022

Liming Yan, Yucen Huang, Yixiao Liu, Ji Ge, Shan Gao, Liping Tan, Lu Liu, Zhenyu Liu, Sihan Ye, Junbo Wang, Jiangran Xiong, Yu Zhou, Hesheng Zhao, Xiaoyue Zhao, Luke W Guddat, Yan Gao, Lan Zhu, Zihe Rao, Zhiyong Lou

{"title":"Structural basis for the concurrence of template recycling and RNA capping in SARS-CoV-2.","authors":"Liming Yan, Yucen Huang, Yixiao Liu, Ji Ge, Shan Gao, Liping Tan, Lu Liu, Zhenyu Liu, Sihan Ye, Junbo Wang, Jiangran Xiong, Yu Zhou, Hesheng Zhao, Xiaoyue Zhao, Luke W Guddat, Yan Gao, Lan Zhu, Zihe Rao, Zhiyong Lou","doi":"10.1016/j.cell.2025.09.022","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.022","url":null,"abstract":"In the SARS-CoV-2 replication-transcription complex (RTC), the nascent template-product duplex is unwound into a template strand for recycling and a product strand that needs to be capped. Here, we determined structures of the SARS-CoV-2 RTC in the pre- and post-capping initiation (CI) states. In the pre-CI state, the RTC has a dimer-of-dimeric architecture (ddRTC). The upstream RNA duplex in one RTC is reciprocally unwound by a helicase in a head-to-head-positioned RTC in the 3'-5' direction. The helicases bind either ADP or ADP⋅Pi in their ATP-binding pockets, suggesting a mechanism for ATP-hydrolysis-driven unwinding. In the post-CI state, the binding of nsp9 to the nsp12 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) disrupts the ddRTC. The N terminus of nsp9 and the triphosphorylated 5' end of the product strand co-localize in NiRAN's catalytic site, exhibiting the state prior to nsp9 RNAylation for capping. These results provide an insight into the concurrence of template recycling and RNA capping in the SARS-CoV-2 RTC.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353975","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

Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome.

IF 42.5 1区生物学

Cell Pub Date : 2025-10-22 DOI: 10.1016/j.cell.2025.09.014

Miguel A Garcia-Campos, Joe Georgeson, Ronit Nir, Robert Reichelt, Kristin A Fluke, Donna Matzov, Vinithra Iyer, Brett W Burkhart, Lauren Lui, Anatoly Kustanovich, Felix Grünberger, Supuni Thalalla-Gamage, Shereen A Howpay-Manage, Milan Gerovac, Nicolas Alexandre, Yuko Nobe, Jakub S Nowak, Manoj Perera, Alexander Apostle, Shiyue Fang, Sebastian Glatt, Ghil Jona, Sébastien Ferreira-Cerca, Jörg Vogel, Masato Taoka, Jordan L Meier, Eric Westhof, Thomas J Santangelo, Dina Grohmann, Moran Shalev-Benami, Schraga Schwartz

{"title":"Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome.","authors":"Miguel A Garcia-Campos, Joe Georgeson, Ronit Nir, Robert Reichelt, Kristin A Fluke, Donna Matzov, Vinithra Iyer, Brett W Burkhart, Lauren Lui, Anatoly Kustanovich, Felix Grünberger, Supuni Thalalla-Gamage, Shereen A Howpay-Manage, Milan Gerovac, Nicolas Alexandre, Yuko Nobe, Jakub S Nowak, Manoj Perera, Alexander Apostle, Shiyue Fang, Sebastian Glatt, Ghil Jona, Sébastien Ferreira-Cerca, Jörg Vogel, Masato Taoka, Jordan L Meier, Eric Westhof, Thomas J Santangelo, Dina Grohmann, Moran Shalev-Benami, Schraga Schwartz","doi":"10.1016/j.cell.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.014","url":null,"abstract":"Ribosomal RNA (rRNA) constitutes the core of ribosomes and is extensively chemically modified. Technical challenges have precluded systematically dissecting rRNA modifications and their dynamics. We develop Pan-Mod-seq, permitting inference of 16 distinct modifications across dozens of samples in parallel. We applied Pan-Mod-seq to RNA from 14 species spanning all domains of life, cultured under highly diverse conditions. While dynamic modifications are rare in mesophiles, in extreme hyperthermophiles, ∼50% of modifications are dynamic. We dissect the biogenesis and function of a conserved module of tandem m5C-ac4C modifications, co-induced at high temperatures, via enzymes intrinsically regulated by temperature and required for growth at higher temperatures. Cryo-electron microscopy (cryo-EM) structures of ribosomes from wild-type (WT) and enzyme-deficient archaea reveal recurrent molecular interactions through which they confer structural stability, and biophysical studies demonstrate their synergistic thermostabilizing role. Our findings systematically dissect rRNA modification plasticity and pave the way for surveying the rRNA epitranscriptome in health and disease.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":""},"PeriodicalIF":42.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353930","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

CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success CRATER肿瘤龛促进CD8+ T细胞参与，并与免疫治疗的成功相对应

IF 64.5 1区生物学

Cell Pub Date : 2025-10-17 DOI: 10.1016/j.cell.2025.09.021

Aya Ludin, Georgia L. Stirtz, Asaf Tal, Ajit J. Nirmal, Kathleen L. Pfaff, Michael Manos, Naomi Besson, Nebiyat Eskndir, Billie Porter, Stephanie M. Jones, Hannah M. Faulkner, Qiyu Gong, Sophia Liu, Irving Barrera, Lijian Wu, Cecilia Pessoa Rodrigues, Aditi Sahu, Elizabeth Jerison, Joao V. Alessi, Biagio Ricciuti, Leonard I. Zon

{"title":"CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success","authors":"Aya Ludin, Georgia L. Stirtz, Asaf Tal, Ajit J. Nirmal, Kathleen L. Pfaff, Michael Manos, Naomi Besson, Nebiyat Eskndir, Billie Porter, Stephanie M. Jones, Hannah M. Faulkner, Qiyu Gong, Sophia Liu, Irving Barrera, Lijian Wu, Cecilia Pessoa Rodrigues, Aditi Sahu, Elizabeth Jerison, Joao V. Alessi, Biagio Ricciuti, Leonard I. Zon","doi":"10.1016/j.cell.2025.09.021","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.021","url":null,"abstract":"T cell-mediated tumor killing underlies immunotherapy success. Here, we used long-term in vivo imaging and high-resolution spatial transcriptomics of zebrafish endogenous melanoma, as well as multiplex imaging of human melanoma, to identify domains facilitating the immune response during immunotherapy. We identified cancer regions of antigen presentation and T cell engagement and retention (CRATERs) as pockets at the stroma-melanocyte boundaries of zebrafish and human melanoma. CRATERs are rich in antigen-recognition molecules, harboring the highest density of CD8+ T cells in tumors. In zebrafish, CD8+ T cells formed prolonged interactions with melanoma cells within CRATERs, characteristic of antigen recognition. Following immunostimulatory treatment, CRATERs expanded, becoming the major sites of activated CD8+ T cell accumulation and tumor killing. In humans, elevation in CRATER density in biopsies following immune checkpoint blockade (ICB) therapy correlated with a clinical response to therapy. CRATERs are structures that show active tumor killing and may be useful as a diagnostic indicator for immunotherapy success.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"27 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306207","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

CRISPR meets AI-based robotics: Advancing sustainable agriculture CRISPR与人工智能机器人：推进可持续农业

IF 64.5 1区生物学

Cell Pub Date : 2025-10-16 DOI: 10.1016/j.cell.2025.09.011

Fabienne Gehrke, Holger Puchta

引用次数: 0

De novo designed voltage-gated anion channels suppress neuron firing 重新设计电压门控阴离子通道抑制神经元放电

IF 64.5 1区生物学

Cell Pub Date : 2025-10-16 DOI: 10.1016/j.cell.2025.09.023

Chen Zhou, Huican Li, Jiaxing Wang, Cheng Qian, Hui Xiong, Zhilin Chu, Qiming Shao, Xuan Li, Shijin Sun, Ke Sun, Aiqin Zhu, Jiawei Wang, Xueqin Jin, Fan Yang, Tamer M. Gamal El-Din, Bo Li, Jing Huang, Kun Wu, Peilong Lu

{"title":"De novo designed voltage-gated anion channels suppress neuron firing","authors":"Chen Zhou, Huican Li, Jiaxing Wang, Cheng Qian, Hui Xiong, Zhilin Chu, Qiming Shao, Xuan Li, Shijin Sun, Ke Sun, Aiqin Zhu, Jiawei Wang, Xueqin Jin, Fan Yang, Tamer M. Gamal El-Din, Bo Li, Jing Huang, Kun Wu, Peilong Lu","doi":"10.1016/j.cell.2025.09.023","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.023","url":null,"abstract":"Design of ion channels responsive to environmental cues has significant implications in modulating cellular activities and sensor development, but it remains a significant challenge due to the complexities involved in designing stimuli-induced conformational changes in proteins. Here, we report the accurate de novo design of voltage-gated anion channels, namely dVGACs. dVGACs adopt a 15-helix pentameric architecture featuring arginine constrictions within the transmembrane span and show voltage-dependent anions currents in patch-clamp experiments. Cryo-electron microscopy (cryo-EM) structures of dVGACs closely align with the design models. Cryo-EM structures and molecular dynamics simulations suggest that the arginine constrictions undergo voltage-induced conformational changes, serving as both a voltage sensor and a selectivity filter as designed. Notably, the anion selectivity and voltage sensitivity of dVGACs can be tuned through targeted mutations for suppressing neuronal firing in situ. The ability to create ion channels with custom-designed conformational changes refreshes our insights into membrane biophysics and unveils diverse potential applications.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"93 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295528","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

Long shared haplotypes identify the southern Urals as a primary source for the 10th-century Hungarians 长期共享的单倍型确定乌拉尔南部是10世纪匈牙利人的主要来源

IF 64.5 1区生物学

Cell Pub Date : 2025-10-16 DOI: 10.1016/j.cell.2025.09.002

Balázs Gyuris, Leonid Vyazov, Attila Türk, Pavel Flegontov, Bea Szeifert, Péter Langó, Balázs Gusztáv Mende, Veronika Csáky, Andrey A. Chizhevskiy, Ilgizar R. Gazimzyanov, Aleksandr A. Khokhlov, Aleksandr G. Kolonskikh, Natalia P. Matveeva, Rida R. Ruslanova, Marina P. Rykun, Ayrat Sitdikov, Elizaveta V. Volkova, Sergei G. Botalov, Dmitriy G. Bugrov, Ivan V. Grudochko, Anna Szécsényi-Nagy

{"title":"Long shared haplotypes identify the southern Urals as a primary source for the 10th-century Hungarians","authors":"Balázs Gyuris, Leonid Vyazov, Attila Türk, Pavel Flegontov, Bea Szeifert, Péter Langó, Balázs Gusztáv Mende, Veronika Csáky, Andrey A. Chizhevskiy, Ilgizar R. Gazimzyanov, Aleksandr A. Khokhlov, Aleksandr G. Kolonskikh, Natalia P. Matveeva, Rida R. Ruslanova, Marina P. Rykun, Ayrat Sitdikov, Elizaveta V. Volkova, Sergei G. Botalov, Dmitriy G. Bugrov, Ivan V. Grudochko, Anna Szécsényi-Nagy","doi":"10.1016/j.cell.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.002","url":null,"abstract":"The origins of the early medieval Magyars who appeared in the Carpathian Basin by the end of the 9th century CE remain incompletely understood. Previous archaeogenetic research identified the newcomers as migrants from the Eurasian steppe. However, genome-wide ancient DNA from putative source populations has not been available to test alternative theories of their precise source. We generated genome-wide ancient DNA data for 131 individuals from archaeological sites in the Ural region in northern Eurasia, which are candidates for the source based on historical, linguistic, and archaeological evidence. Our results tightly link the Magyars to people of the early medieval Karayakupovo archaeological horizon on both the European and Asian sides of the southern Urals. The ancestors of the people of the Karayakupovo archaeological horizon were established in the broader Urals by the Late Iron Age, and their descendants persisted in the Volga-Kama region until at least the 14th century.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"2 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295530","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

Exploring Latin America one cell at a time 一次一个细胞地探索拉丁美洲

IF 64.5 1区生物学

Cell Pub Date : 2025-10-16 DOI: 10.1016/j.cell.2025.09.013

Patricia A. Possik, David J. Adams, Flavia C. Aguiar, Tamires Caixeta Alves, Fabíola S. Alves-Hanna, Carlos Mario Restrepo Arboleda, Erick Armingol, Liã Bárbara Arruda, Yesid Cuesta Astroz, Jacqueline M. Boccacino, Danielle C. Bonfim, Juan F. Calderon, Alexis Germán Murillo Carrasco, Danielle G. Carvalho, Benilton S. Carvalho, Paulo Vinícius Sanches Daltro de Carvalho, Alex Castro, Lia Chappell, Ricardo Chinchilla-Monge, Daniela Di Bella, Mariana Boroni

引用次数: 0

Don’t forget to floss! An innovative approach for vaccine delivery 别忘了用牙线！提供疫苗的创新方法

IF 64.5 1区生物学

Cell Pub Date : 2025-10-16 DOI: 10.1016/j.cell.2025.09.008

Heather D. Hickman, Niki M. Moutsopoulos

引用次数: 0

The small GTPase Ran defines nuclear pore complex asymmetry. 小GTPase Ran定义了核孔复合物的不对称性。

IF 42.5 1区生物学

Cell Pub Date : 2025-10-16 Epub Date: 2025-08-18 DOI: 10.1016/j.cell.2025.07.025

Jenny Sachweh, Mandy Börmel, Sven Klumpe, Anja Becker, Reiya Taniguchi, Marta Anna Kubańska, Verena Pintschovius, Eva Kaindl, Jürgen M Plitzko, Florian Wilfling, Martin Beck, Bernhard Hampoelz

{"title":"The small GTPase Ran defines nuclear pore complex asymmetry.","authors":"Jenny Sachweh, Mandy Börmel, Sven Klumpe, Anja Becker, Reiya Taniguchi, Marta Anna Kubańska, Verena Pintschovius, Eva Kaindl, Jürgen M Plitzko, Florian Wilfling, Martin Beck, Bernhard Hampoelz","doi":"10.1016/j.cell.2025.07.025","DOIUrl":"10.1016/j.cell.2025.07.025","url":null,"abstract":"Nuclear pore complexes (NPCs) bridge across the nuclear envelope and mediate nucleocytoplasmic exchange. They consist of hundreds of nucleoporin building blocks and exemplify the structural complexity of macromolecular assemblies. To ensure transport directionality, different nucleoporin complexes are attached to the cytoplasmic and nuclear face of the NPC. How those asymmetric structures are faithfully assembled onto the symmetric scaffold architecture that exposes the same interaction surfaces to either side remained enigmatic. Here, we combine cryo-electron tomography, subtomogram averaging, and template matching with live imaging to address this question in budding yeast and Drosophila. We genetically induce ectopic nuclear pores and show that pores outside the nuclear envelope are symmetric. We furthermore demonstrate that the peripheral NPC configuration is affected by the nucleotide state of the small GTPase Ran. Our findings indicate that the nuclear transport system is self-regulatory, namely that the same molecular mechanism controls both transport and transport channel composition.","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"5931-5946.e16"},"PeriodicalIF":42.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882290","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

Conversion of IscB and Cas9 into RNA-guided RNA editors. IscB和Cas9转化为RNA引导的RNA编辑器。

IF 42.5 1区生物学

Cell Pub Date : 2025-10-16 Epub Date: 2025-08-18 DOI: 10.1016/j.cell.2025.07.032

Chengtao Xu, Xiaolin Niu, Haifeng Sun, Hao Yan, Weixin Tang, Ailong Ke

引用次数: 0