Cell Research最新文献_第10页

Prometheus 2.0: drug-induced liver regeneration arising 普罗米修斯 2.0：药物引起的肝脏再生

IF 28.1 1区生物学

Cell Research Pub Date : 2024-04-29 DOI: 10.1038/s41422-024-00965-w

Jan S. Tchorz

引用次数: 0

Structural insights into human exon-defined spliceosome prior to activation 人类外显子定义剪接体激活前的结构研究。

IF 44.1 1区生物学

Cell Research Pub Date : 2024-04-24 DOI: 10.1038/s41422-024-00949-w

Wenyu Zhang, Xiaofeng Zhang, Xiechao Zhan, Rui Bai, Jianlin Lei, Chuangye Yan, Yigong Shi

{"title":"Structural insights into human exon-defined spliceosome prior to activation","authors":"Wenyu Zhang, Xiaofeng Zhang, Xiechao Zhan, Rui Bai, Jianlin Lei, Chuangye Yan, Yigong Shi","doi":"10.1038/s41422-024-00949-w","DOIUrl":"10.1038/s41422-024-00949-w","url":null,"abstract":"Spliceosome is often assembled across an exon and undergoes rearrangement to span a neighboring intron. Most states of the intron-defined spliceosome have been structurally characterized. However, the structure of a fully assembled exon-defined spliceosome remains at large. During spliceosome assembly, the pre-catalytic state (B complex) is converted from its precursor (pre-B complex). Here we report atomic structures of the exon-defined human spliceosome in four sequential states: mature pre-B, late pre-B, early B, and mature B. In the previously unknown late pre-B state, U1 snRNP is already released but the remaining proteins are still in the pre-B state; unexpectedly, the RNAs are in the B state, with U6 snRNA forming a duplex with 5′-splice site and U5 snRNA recognizing the 3′-end of the exon. In the early and mature B complexes, the B-specific factors are stepwise recruited and specifically recognize the exon 3′-region. Our study reveals key insights into the assembly of the exon-defined spliceosomes and identifies mechanistic steps of the pre-B-to-B transition.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 6","pages":"428-439"},"PeriodicalIF":44.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00949-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661797","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

Human tumor suppressor PDCD4 directly interacts with ribosomes to repress translation 人类肿瘤抑制因子 PDCD4 与核糖体直接相互作用抑制翻译

IF 28.1 1区生物学

Cell Research Pub Date : 2024-04-19 DOI: 10.1038/s41422-024-00962-z

Xianwen Ye, Zixuan Huang, Yi Li, Mengjiao Wang, Wanyu Meng, Maojian Miao, Jingdong Cheng

引用次数: 0

Structural basis for the recognition of HCoV-HKU1 by human TMPRSS2 人类 TMPRSS2 识别 HCoV-HKU1 的结构基础

IF 28.1 1区生物学

Cell Research Pub Date : 2024-04-19 DOI: 10.1038/s41422-024-00958-9

Lingyun Xia, Yuanyuan Zhang, Qiang Zhou

引用次数: 0

Peripheral cancer remodeling of central neural system 重塑中枢神经系统的外周癌症

IF 44.1 1区生物学

Cell Research Pub Date : 2024-04-12 DOI: 10.1038/s41422-024-00960-1

Gray Umbach, Shawn L. Hervey-Jumper

引用次数: 0

APOE3ch alleviates Aβ and tau pathology and neurodegeneration in the human APPNL-G-F cerebral organoid model of Alzheimer’s disease APOE3ch 可减轻人类 APPNL-G-F 阿尔茨海默病脑器官模型中 Aβ 和 tau 的病理变化及神经退行性变

IF 44.1 1区生物学

Cell Research Pub Date : 2024-04-12 DOI: 10.1038/s41422-024-00957-w

Hang Liu, Fan Mei, Rongrong Ye, Xinyu Han, Shudan Wang, Yan Ding, Yun Zhi, Keliang Pang, Wei Guo, Bai Lu

引用次数: 0

Structural basis for human Cav3.2 inhibition by selective antagonists 人类 Cav3.2 受选择性拮抗剂抑制的结构基础

IF 44.1 1区生物学

Cell Research Pub Date : 2024-04-11 DOI: 10.1038/s41422-024-00959-8

Jian Huang, Xiao Fan, Xueqin Jin, Chen Lyu, Qinmeng Guo, Tao Liu, Jiaofeng Chen, Amaël Davakan, Philippe Lory, Nieng Yan

{"title":"Structural basis for human Cav3.2 inhibition by selective antagonists","authors":"Jian Huang, Xiao Fan, Xueqin Jin, Chen Lyu, Qinmeng Guo, Tao Liu, Jiaofeng Chen, Amaël Davakan, Philippe Lory, Nieng Yan","doi":"10.1038/s41422-024-00959-8","DOIUrl":"10.1038/s41422-024-00959-8","url":null,"abstract":"The Cav3.2 subtype of T-type calcium channels has been targeted for developing analgesics and anti-epileptics for its role in pain and epilepsy. Here we present the cryo-EM structures of Cav3.2 alone and in complex with four T-type calcium channel selective antagonists with overall resolutions ranging from 2.8 Å to 3.2 Å. The four compounds display two binding poses. ACT-709478 and TTA-A2 both place their cyclopropylphenyl-containing ends in the central cavity to directly obstruct ion flow, meanwhile extending their polar tails into the IV-I fenestration. TTA-P2 and ML218 project their 3,5-dichlorobenzamide groups into the II-III fenestration and place their hydrophobic tails in the cavity to impede ion permeation. The fenestration-penetrating mode immediately affords an explanation for the state-dependent activities of these antagonists. Structure-guided mutational analysis identifies several key residues that determine the T-type preference of these drugs. The structures also suggest the role of an endogenous lipid in stabilizing drug binding in the central cavity.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 6","pages":"440-450"},"PeriodicalIF":44.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00959-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580621","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

System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning 通过大规模钙成像和机器学习揭示丘脑上核的系统级时间计算和表征

IF 28.1 1区生物学

Cell Research Pub Date : 2024-04-11 DOI: 10.1038/s41422-024-00956-x

Zichen Wang, Jing Yu, Muyue Zhai, Zehua Wang, Kaiwen Sheng, Yu Zhu, Tianyu Wang, Mianzhi Liu, Lu Wang, Miao Yan, Jue Zhang, Ying Xu, Xianhua Wang, Lei Ma, Wei Hu, Heping Cheng

{"title":"System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning","authors":"Zichen Wang, Jing Yu, Muyue Zhai, Zehua Wang, Kaiwen Sheng, Yu Zhu, Tianyu Wang, Mianzhi Liu, Lu Wang, Miao Yan, Jue Zhang, Ying Xu, Xianhua Wang, Lei Ma, Wei Hu, Heping Cheng","doi":"10.1038/s41422-024-00956-x","DOIUrl":"10.1038/s41422-024-00956-x","url":null,"abstract":"The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca2+ signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN. Specifically, we developed a high-speed dual-view two-photon microscope for volumetric Ca2+ imaging of up to 9000 GABAergic neurons in adult SCN slices, and leveraged machine learning methods to capture emergent properties from multiscale Ca2+ signals as a whole. We achieved hourly time prediction by polling random cohorts of SCN neurons, reaching 99.0% accuracy at a cohort size of 900. Further, we revealed that functional neuron subtypes identified by contrastive learning tend to aggregate separately in the SCN space, giving rise to bilaterally symmetrical ripple-like modular patterns. Individual modules represent distinctive time features, such that a module-specifically learned time predictor can also accurately decode hourly time from random polling of the same module. These findings open a new paradigm in deciphering the design principle of the biological clock at the system level.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 7","pages":"493-503"},"PeriodicalIF":28.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00956-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547759","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

Author Correction: Substrate and drug recognition mechanisms of SLC19A3 作者更正：SLC19A3 的底物和药物识别机制。

IF 44.1 1区生物学

Cell Research Pub Date : 2024-04-05 DOI: 10.1038/s41422-024-00953-0

Yu Dang, Tianyi Zhang, Shabareesh Pidathala, Guopeng Wang, Yijie Wang, Nanhao Chen, Chen Song, Chia-Hsueh Lee, Zhe Zhang

引用次数: 0

Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs 发现由 RAGATH-18 衍生 RNA 引导的 DNA 内切酶及其结构机制

IF 44.1 1区生物学

Cell Research Pub Date : 2024-04-04 DOI: 10.1038/s41422-024-00952-1

Kuan Ren, Fengxia Zhou, Fan Zhang, Mingyu Yin, Yuwei Zhu, Shouyu Wang, Yan Chen, Tengjin Huang, Zixuan Wu, Jiale He, Anqi Zhang, Changyou Guo, Zhiwei Huang

{"title":"Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs","authors":"Kuan Ren, Fengxia Zhou, Fan Zhang, Mingyu Yin, Yuwei Zhu, Shouyu Wang, Yan Chen, Tengjin Huang, Zixuan Wu, Jiale He, Anqi Zhang, Changyou Guo, Zhiwei Huang","doi":"10.1038/s41422-024-00952-1","DOIUrl":"10.1038/s41422-024-00952-1","url":null,"abstract":"CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 5","pages":"370-385"},"PeriodicalIF":44.1,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00952-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349225","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