Molecular Cell最新文献_第9页

Base-resolution m5C profiling across the mammalian transcriptome by bisulfite-free enzyme-assisted chemical labeling approach 通过无亚硫酸氢盐酶辅助化学标记法对哺乳动物转录组进行基底分辨率 m5C 分析

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-12 DOI: 10.1016/j.molcel.2024.06.021

Liang Lu, Xiaoting Zhang, Yuenan Zhou, Zuokun Shi, Xiwen Xie, Xinyue Zhang, Liaoliao Gao, Anbo Fu, Cong Liu, Bo He, Xushen Xiong, Yafei Yin, Qingqing Wang, Chengqi Yi, Xiaoyu Li

{"title":"Base-resolution m5C profiling across the mammalian transcriptome by bisulfite-free enzyme-assisted chemical labeling approach","authors":"Liang Lu, Xiaoting Zhang, Yuenan Zhou, Zuokun Shi, Xiwen Xie, Xinyue Zhang, Liaoliao Gao, Anbo Fu, Cong Liu, Bo He, Xushen Xiong, Yafei Yin, Qingqing Wang, Chengqi Yi, Xiaoyu Li","doi":"10.1016/j.molcel.2024.06.021","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.021","url":null,"abstract":"5-methylcytosine (m5C) is a prevalent RNA modification crucial for gene expression regulation. However, accurate and sensitive m5C sites identification remains challenging due to severe RNA degradation and reduced sequence complexity during bisulfite sequencing (BS-seq). Here, we report m5C-TAC-seq, a bisulfite-free approach combining TET-assisted m5C-to-f5C oxidation with selective chemical labeling, therefore enabling direct base-resolution m5C detection through pre-enrichment and C-to-T transitions at m5C sites. With m5C-TAC-seq, we comprehensively profiled the m5C methylomes in human and mouse cells, identifying a substantially larger number of confident m5C sites. Through perturbing potential m5C methyltransferases, we deciphered the responsible enzymes for most m5C sites, including the characterization of NSUN5’s involvement in mRNA m5C deposition. Additionally, we characterized m5C dynamics during mESC differentiation. Notably, the mild reaction conditions and preservation of nucleotide composition in m5C-TAC-seq allow m5C detection in chromatin-associated RNAs. The accurate and robust m5C-TAC-seq will advance research into m5C methylation functional investigation.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597345","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

Thrifty tissues prefer recycled purines over new-cleotides 节俭的组织更喜欢回收的嘌呤而不是新的核苷酸

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.015

David Sokolov, Lucas B. Sullivan

引用次数: 0

Dynamic BTB-domain filaments promote clustering of ZBTB proteins 动态 BTB-结构域丝促进 ZBTB 蛋白的聚集

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.05.029

Lucija Mance, Nicolas Bigot, Edison Zhamungui Sánchez, Franck Coste, Natalia Martín-González, Siham Zentout, Marin Biliškov, Zofia Pukało, Aanchal Mishra, Catherine Chapuis, Ana-Andreea Arteni, Axelle Lateur, Stéphane Goffinont, Virginie Gaudon, Ibtissam Talhaoui, Ignacio Casuso, Martine Beaufour, Norbert Garnier, Franck Artzner, Martine Cadene, Marcin Józef Suskiewicz

{"title":"Dynamic BTB-domain filaments promote clustering of ZBTB proteins","authors":"Lucija Mance, Nicolas Bigot, Edison Zhamungui Sánchez, Franck Coste, Natalia Martín-González, Siham Zentout, Marin Biliškov, Zofia Pukało, Aanchal Mishra, Catherine Chapuis, Ana-Andreea Arteni, Axelle Lateur, Stéphane Goffinont, Virginie Gaudon, Ibtissam Talhaoui, Ignacio Casuso, Martine Beaufour, Norbert Garnier, Franck Artzner, Martine Cadene, Marcin Józef Suskiewicz","doi":"10.1016/j.molcel.2024.05.029","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.05.029","url":null,"abstract":"The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588742","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

Meet the authors: Mei-Sheng Xiao, Arun Prasath Damodaran, and Thomas Gonatopoulos-Pournatzis 与作者见面肖梅生、Arun Prasath Damodaran 和 Thomas Gonatopoulos-Pournatzis

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.019

Mei-Sheng Xiao, Arun Prasath Damodaran, Thomas Gonatopoulos-Pournatzis

引用次数: 0

Chaperones in concert: Orchestrating co-translational protein folding in the cell 伴侣协同作用：协调细胞中蛋白质的共翻译折叠

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.018

Bob Schiffrin, Antonio N. Calabrese

引用次数: 0

Assigning function to an unexplored Integrator module 为未开发的集成器模块分配功能

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.014

William Garland, Jérôme O. Rouvière, Torben Heick Jensen

引用次数: 0

The molecular basis of tRNA selectivity by human pseudouridine synthase 3 人假尿苷合成酶 3 选择性 tRNA 的分子基础

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.013

Ting-Yu Lin, Leon Kleemann, Jakub Jeżowski, Dominika Dobosz, Michał Rawski, Paulina Indyka, Grzegorz Ważny, Rahul Mehta, Andrzej Chramiec-Głąbik, Łukasz Koziej, Tristan Ranff, Christian Fufezan, Mateusz Wawro, Jakub Kochan, Joanna Bereta, Sebastian A. Leidel, Sebastian Glatt

{"title":"The molecular basis of tRNA selectivity by human pseudouridine synthase 3","authors":"Ting-Yu Lin, Leon Kleemann, Jakub Jeżowski, Dominika Dobosz, Michał Rawski, Paulina Indyka, Grzegorz Ważny, Rahul Mehta, Andrzej Chramiec-Głąbik, Łukasz Koziej, Tristan Ranff, Christian Fufezan, Mateusz Wawro, Jakub Kochan, Joanna Bereta, Sebastian A. Leidel, Sebastian Glatt","doi":"10.1016/j.molcel.2024.06.013","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.013","url":null,"abstract":"Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588737","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

Polymerization of ZBTB transcription factors regulates chromatin occupancy ZBTB转录因子的聚合调节染色质占有率

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.010

Paul M.C. Park, Jiho Park, Jared Brown, Moritz Hunkeler, Shourya S. Roy Burman, Katherine A. Donovan, Hojong Yoon, Radosław P. Nowak, Mikołaj Słabicki, Benjamin L. Ebert, Eric S. Fischer

{"title":"Polymerization of ZBTB transcription factors regulates chromatin occupancy","authors":"Paul M.C. Park, Jiho Park, Jared Brown, Moritz Hunkeler, Shourya S. Roy Burman, Katherine A. Donovan, Hojong Yoon, Radosław P. Nowak, Mikołaj Słabicki, Benjamin L. Ebert, Eric S. Fischer","doi":"10.1016/j.molcel.2024.06.010","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.010","url":null,"abstract":"BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6’s broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588740","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

Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1 基于结构的 SHMT1 代谢酶核糖调节机制

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-11 DOI: 10.1016/j.molcel.2024.06.016

Sharon Spizzichino, Federica Di Fonzo, Chiara Marabelli, Angela Tramonti, Antonio Chaves-Sanjuan, Alessia Parroni, Giovanna Boumis, Francesca Romana Liberati, Alessio Paone, Linda Celeste Montemiglio, Matteo Ardini, Arjen J. Jakobi, Alok Bharadwaj, Paolo Swuec, Gian Gaetano Tartaglia, Alessandro Paiardini, Roberto Contestabile, Antonello Mai, Dante Rotili, Francesco Fiorentino, Francesca Cutruzzolà

{"title":"Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1","authors":"Sharon Spizzichino, Federica Di Fonzo, Chiara Marabelli, Angela Tramonti, Antonio Chaves-Sanjuan, Alessia Parroni, Giovanna Boumis, Francesca Romana Liberati, Alessio Paone, Linda Celeste Montemiglio, Matteo Ardini, Arjen J. Jakobi, Alok Bharadwaj, Paolo Swuec, Gian Gaetano Tartaglia, Alessandro Paiardini, Roberto Contestabile, Antonello Mai, Dante Rotili, Francesco Fiorentino, Francesca Cutruzzolà","doi":"10.1016/j.molcel.2024.06.016","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.016","url":null,"abstract":"RNA can directly control protein activity in a process called riboregulation; only a few mechanisms of riboregulation have been described in detail, none of which have been characterized on structural grounds. Here, we present a comprehensive structural, functional, and phylogenetic analysis of riboregulation of cytosolic serine hydroxymethyltransferase (SHMT1), the enzyme interconverting serine and glycine in one-carbon metabolism. We have determined the cryoelectron microscopy (cryo-EM) structure of human SHMT1 in its free- and RNA-bound states, and we show that the RNA modulator competes with polyglutamylated folates and acts as an allosteric switch, selectively altering the enzyme’s reactivity vs. serine. In addition, we identify the tetrameric assembly and a flap structural motif as key structural elements necessary for binding of RNA to eukaryotic SHMT1. The results presented here suggest that riboregulation may have played a role in evolution of eukaryotic SHMT1 and in compartmentalization of one-carbon metabolism. Our findings provide insights for RNA-based therapeutic strategies targeting this cancer-linked metabolic pathway.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588777","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

Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress 六磷酸酶 1 形成环，在能量胁迫期间调节线粒体裂变

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-08 DOI: 10.1016/j.molcel.2024.06.009

Johannes Pilic, Benjamin Gottschalk, Benjamin Bourgeois, Hansjörg Habisch, Zhanat Koshenov, Furkan E. Oflaz, Yusuf C. Erdogan, Seyed M. Miri, Esra N. Yiğit, Mehmet Ş. Aydın, Gürkan Öztürk, Emrah Eroglu, Varda Shoshan-Barmatz, Tobias Madl, Wolfgang F. Graier, Roland Malli

{"title":"Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress","authors":"Johannes Pilic, Benjamin Gottschalk, Benjamin Bourgeois, Hansjörg Habisch, Zhanat Koshenov, Furkan E. Oflaz, Yusuf C. Erdogan, Seyed M. Miri, Esra N. Yiğit, Mehmet Ş. Aydın, Gürkan Öztürk, Emrah Eroglu, Varda Shoshan-Barmatz, Tobias Madl, Wolfgang F. Graier, Roland Malli","doi":"10.1016/j.molcel.2024.06.009","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.009","url":null,"abstract":"Metabolic enzymes can adapt during energy stress, but the consequences of these adaptations remain understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, forms rings around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and mitochondrial dynamics protein (MiD51). HK1-rings prevent mitochondrial fission by displacing the dynamin-related protein 1 (Drp1) from mitochondrial fission factor (Mff) and mitochondrial fission 1 protein (Fis1). The disassembly of HK1-rings during energy restoration correlated with mitochondrial fission. Mechanistically, we identified that the lack of ATP and glucose-6-phosphate (G6P) promotes the formation of HK1-rings. Mutations that affect the formation of HK1-rings showed that HK1-rings rewire cellular metabolism toward increased TCA cycle activity. Our findings highlight that HK1 is an energy stress sensor that regulates the shape, connectivity, and metabolic activity of mitochondria. Thus, the formation of HK1-rings may affect mitochondrial function in energy-stress-related pathologies.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561669","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