Molecular Cell最新文献

Spatial omics advances for in situ RNA biology 空间全息技术在原位 RNA 生物学方面的进展

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-12 DOI: 10.1016/j.molcel.2024.08.002

Jingyi Ren, Shuchen Luo, Hailing Shi, Xiao Wang

引用次数: 0

Resolution of transcription-induced hexasome-nucleosome complexes by Chd1 and FACT 通过 Chd1 和 FACT 分解转录诱导的六聚体-核小体复合物

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-12 DOI: 10.1016/j.molcel.2024.08.022

Maik Engeholm, Johann J. Roske, Elisa Oberbeckmann, Christian Dienemann, Michael Lidschreiber, Patrick Cramer, Lucas Farnung

引用次数: 0

RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages RAPIDASH：无标记核糖体相关蛋白富集揭示胚胎组织、癌细胞和巨噬细胞中的组成动态

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-10 DOI: 10.1016/j.molcel.2024.08.023

Teodorus Theo Susanto, Victoria Hung, Andrew G. Levine, Yuxiang Chen, Craig H. Kerr, Yongjin Yoo, Juan A. Oses-Prieto, Lisa Fromm, Zijian Zhang, Travis C. Lantz, Kotaro Fujii, Marius Wernig, Alma L. Burlingame, Davide Ruggero, Maria Barna

{"title":"RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages","authors":"Teodorus Theo Susanto, Victoria Hung, Andrew G. Levine, Yuxiang Chen, Craig H. Kerr, Yongjin Yoo, Juan A. Oses-Prieto, Lisa Fromm, Zijian Zhang, Travis C. Lantz, Kotaro Fujii, Marius Wernig, Alma L. Burlingame, Davide Ruggero, Maria Barna","doi":"10.1016/j.molcel.2024.08.023","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.023","url":null,"abstract":"Ribosomes are emerging as direct regulators of gene expression, with ribosome-associated proteins (RAPs) allowing ribosomes to modulate translation. Nevertheless, a lack of technologies to enrich RAPs across sample types has prevented systematic analysis of RAP identities, dynamics, and functions. We have developed a label-free methodology called RAPIDASH to enrich ribosomes and RAPs from any sample. We applied RAPIDASH to mouse embryonic tissues and identified hundreds of potential RAPs, including Dhx30 and Llph, two forebrain RAPs important for neurodevelopment. We identified a critical role of LLPH in neural development linked to the translation of genes with long coding sequences. In addition, we showed that RAPIDASH can identify ribosome changes in cancer cells. Finally, we characterized ribosome composition remodeling during immune cell activation and observed extensive changes post-stimulation. RAPIDASH has therefore enabled the discovery of RAPs in multiple cell types, tissues, and stimuli and is adaptable to characterize ribosome remodeling in several contexts.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160994","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

Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity 靶向 APT2 可改善 MAVS 棕榈酰化和抗病毒先天免疫力

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-09 DOI: 10.1016/j.molcel.2024.08.014

Lang Bu, Huan Wang, Shuishen Zhang, Yi Zhang, Miaowen Liu, Zhengkun Zhang, Xueji Wu, Qiwei Jiang, Lei Wang, Wei Xie, Miao He, Zhengran Zhou, Chao Cheng, Jianping Guo

{"title":"Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity","authors":"Lang Bu, Huan Wang, Shuishen Zhang, Yi Zhang, Miaowen Liu, Zhengkun Zhang, Xueji Wu, Qiwei Jiang, Lei Wang, Wei Xie, Miao He, Zhengran Zhou, Chao Cheng, Jianping Guo","doi":"10.1016/j.molcel.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.014","url":null,"abstract":"Innate immunity serves as the primary defense against viral and microbial infections in humans. The precise influence of cellular metabolites, especially fatty acids, on antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a key modulator of antiviral infections in human cells. Mechanistically, PA induces mitochondrial antiviral signaling protein (MAVS) palmitoylation, aggregation, and subsequent activation, thereby enhancing the innate immune response. The palmitoyl-transferase ZDHHC24 catalyzes MAVS palmitoylation, thereby boosting the TBK1-IRF3-interferon (IFN) pathway, particularly under conditions of PA stimulation or high-fat-diet-fed mouse models, leading to antiviral immune responses. Additionally, APT2 de-palmitoylates MAVS, thus inhibiting antiviral signaling, suggesting that its inhibitors, such as ML349, effectively reverse MAVS activation in response to antiviral infections. These findings underscore the critical role of PA in regulating antiviral innate immunity through MAVS palmitoylation and provide strategies for enhancing PA intake or targeting APT2 for combating viral infections.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158709","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

Heterochromatin: Hiding from the remodeling machines 异染色质：躲避重塑机器的攻击

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-05 DOI: 10.1016/j.molcel.2024.08.012

Craig L. Peterson

引用次数: 0

Anti-CRISPRs deconstruct bacterial defense 抗CRISPR解构细菌防御系统

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-05 DOI: 10.1016/j.molcel.2024.08.008

Nils Birkholz, Peter C. Fineran

引用次数: 0

RNA polymerases reshape chromatin architecture and couple transcription on individual fibers. RNA 聚合酶重塑染色质结构，并将转录耦合到单个纤维上。

IF 14.5 1区生物学

Molecular Cell Pub Date : 2024-09-05 Epub Date: 2024-08-26 DOI: 10.1016/j.molcel.2024.08.013

Thomas W Tullius, R Stefan Isaac, Danilo Dubocanin, Jane Ranchalis, L Stirling Churchman, Andrew B Stergachis

{"title":"RNA polymerases reshape chromatin architecture and couple transcription on individual fibers.","authors":"Thomas W Tullius, R Stefan Isaac, Danilo Dubocanin, Jane Ranchalis, L Stirling Churchman, Andrew B Stergachis","doi":"10.1016/j.molcel.2024.08.013","DOIUrl":"10.1016/j.molcel.2024.08.013","url":null,"abstract":"RNA polymerases must initiate and pause within a complex chromatin environment, surrounded by nucleosomes and other transcriptional machinery. This environment creates a spatial arrangement along individual chromatin fibers ripe for both competition and coordination, yet these relationships remain largely unknown owing to the inherent limitations of traditional structural and sequencing methodologies. To address this, we employed long-read chromatin fiber sequencing (Fiber-seq) in Drosophila to visualize RNA polymerase (Pol) within its native chromatin context with single-molecule precision along up to 30 kb fibers. We demonstrate that Fiber-seq enables the identification of individual Pol II, nucleosome, and transcription factor footprints, revealing Pol II pausing-driven destabilization of downstream nucleosomes. Furthermore, we demonstrate pervasive direct distance-dependent transcriptional coupling between nearby Pol II genes, Pol III genes, and transcribed enhancers, modulated by local chromatin architecture. Overall, transcription initiation reshapes surrounding nucleosome architecture and couples nearby transcriptional machinery along individual chromatin fibers.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":14.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080926","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

Proteasomes safeguard the plant stress granule homeostasis 蛋白酶体保障植物应激颗粒的平衡

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-05 DOI: 10.1016/j.molcel.2024.08.011

Qi Chen, Xiaoxin Chen, Peiguo Yang

引用次数: 0

Mechanisms controlling replication fork stalling and collapse at topoisomerase 1 cleavage complexes 控制拓扑异构酶 1 分裂复合物复制叉停滞和崩溃的机制

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-04 DOI: 10.1016/j.molcel.2024.08.004

Rose Westhorpe, Johann J. Roske, Joseph T.P. Yeeles

{"title":"Mechanisms controlling replication fork stalling and collapse at topoisomerase 1 cleavage complexes","authors":"Rose Westhorpe, Johann J. Roske, Joseph T.P. Yeeles","doi":"10.1016/j.molcel.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.004","url":null,"abstract":"Topoisomerase 1 cleavage complexes (Top1-ccs) comprise a DNA-protein crosslink and a single-stranded DNA break that can significantly impact the DNA replication machinery (replisome). Consequently, inhibitors that trap Top1-ccs are used extensively in research and clinical settings to generate DNA replication stress, yet how the replisome responds upon collision with a Top1-cc remains obscure. By reconstituting collisions between budding yeast replisomes, assembled from purified proteins, and site-specific Top1-ccs, we have uncovered mechanisms underlying replication fork stalling and collapse. We find that stalled replication forks are surprisingly stable and that their stability is influenced by the template strand that Top1 is crosslinked to, the fork protection complex proteins Tof1-Csm3 (human TIMELESS-TIPIN), and the convergence of replication forks. Moreover, nascent-strand mapping and cryoelectron microscopy (cryo-EM) of stalled forks establishes replisome remodeling as a key factor in the initial response to Top1-ccs. These findings have important implications for the use of Top1 inhibitors in research and in the clinic.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130745","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 high-light-sensitivity mechanism and optogenetic properties of the bacteriorhodopsin-like channelrhodopsin GtCCR4 类细菌视紫红质通道视紫红质 GtCCR4 的高光敏机制和光遗传特性

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-03 DOI: 10.1016/j.molcel.2024.08.016

Tatsuki Tanaka, Shoko Hososhima, Yo Yamashita, Teppei Sugimoto, Toshiki Nakamura, Shunta Shigemura, Wataru Iida, Fumiya K. Sano, Kazumasa Oda, Takayuki Uchihashi, Kota Katayama, Yuji Furutani, Satoshi P. Tsunoda, Wataru Shihoya, Hideki Kandori, Osamu Nureki

{"title":"The high-light-sensitivity mechanism and optogenetic properties of the bacteriorhodopsin-like channelrhodopsin GtCCR4","authors":"Tatsuki Tanaka, Shoko Hososhima, Yo Yamashita, Teppei Sugimoto, Toshiki Nakamura, Shunta Shigemura, Wataru Iida, Fumiya K. Sano, Kazumasa Oda, Takayuki Uchihashi, Kota Katayama, Yuji Furutani, Satoshi P. Tsunoda, Wataru Shihoya, Hideki Kandori, Osamu Nureki","doi":"10.1016/j.molcel.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.016","url":null,"abstract":"Channelrhodopsins are microbial light-gated ion channels that can control the firing of neurons in response to light. Among several cation channelrhodopsins identified in Guillardia theta (GtCCRs), GtCCR4 has higher light sensitivity than typical channelrhodopsins. Furthermore, GtCCR4 shows superior properties as an optogenetic tool, such as minimal desensitization. Our structural analyses of GtCCR2 and GtCCR4 revealed that GtCCR4 has an outwardly bent transmembrane helix, resembling the conformation of activated G-protein-coupled receptors. Spectroscopic and electrophysiological comparisons suggested that this helix bend in GtCCR4 omits channel recovery time and contributes to high light sensitivity. An electrophysiological comparison of GtCCR4 and the well-characterized optogenetic tool ChRmine demonstrated that GtCCR4 has superior current continuity and action-potential spike generation with less invasiveness in neurons. We also identified highly active mutants of GtCCR4. These results shed light on the diverse structures and dynamics of microbial rhodopsins and demonstrate the strong optogenetic potential of GtCCR4.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123930","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