Molecular Cell最新文献_第8页

Emerging and re-emerging themes in co-transcriptional pre-mRNA splicing 共转录前 mRNA 剪接中新出现和再次出现的主题

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-03 DOI: 10.1016/j.molcel.2024.08.036

Tucker J. Carrocci, Karla M. Neugebauer

引用次数: 0

Understanding nuclear mRNA export: Survival under stress 了解核 mRNA 的输出：压力下的生存

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-03 DOI: 10.1016/j.molcel.2024.08.028

Johanna Franziska Seidler, Katja Sträßer

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The many faces of RNA 核糖核酸的多面性

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-03 DOI: 10.1016/j.molcel.2024.09.017

Bryan T. Harada

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An RNA-centric view of transcription and genome organization 以 RNA 为中心的转录和基因组组织视角

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-03 DOI: 10.1016/j.molcel.2024.08.021

Jonathan E. Henninger, Richard A. Young

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Dynamic conformation: Marching toward circular RNA function and application 动态构象：向环形 RNA 的功能和应用迈进

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-03 DOI: 10.1016/j.molcel.2024.08.020

Chu-Xiao Liu, Li Yang, Ling-Ling Chen

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Filament formation activates protease and ring nuclease activities of CRISPR Lon-SAVED 丝状体的形成激活了 CRISPR Lon-SAVED 的蛋白酶和环状核酸酶活性

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-02 DOI: 10.1016/j.molcel.2024.09.002

Dalia Smalakyte, Audrone Ruksenaite, Giedrius Sasnauskas, Giedre Tamulaitiene, Gintautas Tamulaitis

{"title":"Filament formation activates protease and ring nuclease activities of CRISPR Lon-SAVED","authors":"Dalia Smalakyte, Audrone Ruksenaite, Giedrius Sasnauskas, Giedre Tamulaitiene, Gintautas Tamulaitis","doi":"10.1016/j.molcel.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.09.002","url":null,"abstract":"To combat phage infection, type III CRISPR-Cas systems utilize cyclic oligoadenylates (cAn) signaling to activate various auxiliary effectors, including the CRISPR-associated Lon-SAVED protease CalpL, which forms a tripartite effector system together with an anti-σ factor, CalpT, and an ECF-like σ factor, CalpS. Here, we report the characterization of the Candidatus Cloacimonas acidaminovorans CalpL-CalpT-CalpS. We demonstrate that cA4 binding triggers CalpL filament formation and activates it to cleave CalpT within the CalpT-CalpS dimer. This cleavage exposes the CalpT C-degron, which targets it for further degradation by cellular proteases. Consequently, CalpS is released to bind to RNA polymerase, causing growth arrest in E. coli. Furthermore, the CalpL-CalpT-CalpS system is regulated by the SAVED domain of CalpL, which is a ring nuclease that cleaves cA4 in a sequential three-step mechanism. These findings provide key mechanistic details for the activation, proteolytic events, and regulation of the signaling cascade in the type III CRISPR-Cas immunity.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"4 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363100","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

Modulation of fungal phosphate homeostasis by the plant hormone strigolactone 植物激素绞股蓝内酯对真菌磷酸盐平衡的调节作用

IF 16 1区生物学

Molecular Cell Pub Date : 2024-10-01 DOI: 10.1016/j.molcel.2024.09.004

James M. Bradley, Michael Bunsick, George Ly, Bruno Aquino, Flora Zhiqi Wang, Duncan Holbrook-Smith, Shingo Suginoo, Dylan Bradizza, Naoki Kato, Omar As’sadiq, Nina Marsh, Hiroyuki Osada, François-Didier Boyer, Christopher S.P. McErlean, Yuichiro Tsuchiya, Rajagopal Subramaniam, Dario Bonetta, Peter McCourt, Shelley Lumba

{"title":"Modulation of fungal phosphate homeostasis by the plant hormone strigolactone","authors":"James M. Bradley, Michael Bunsick, George Ly, Bruno Aquino, Flora Zhiqi Wang, Duncan Holbrook-Smith, Shingo Suginoo, Dylan Bradizza, Naoki Kato, Omar As’sadiq, Nina Marsh, Hiroyuki Osada, François-Didier Boyer, Christopher S.P. McErlean, Yuichiro Tsuchiya, Rajagopal Subramaniam, Dario Bonetta, Peter McCourt, Shelley Lumba","doi":"10.1016/j.molcel.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.09.004","url":null,"abstract":"Inter-kingdom communication through small molecules is essential to the coexistence of organisms in an ecosystem. In soil communities, the plant root is a nexus of interactions for a remarkable number of fungi and is a source of small-molecule plant hormones that shape fungal compositions. Although hormone signaling pathways are established in plants, how fungi perceive and respond to molecules is unclear because many plant-associated fungi are recalcitrant to experimentation. Here, we develop an approach using the model fungus, Saccharomyces cerevisiae, to elucidate mechanisms of fungal response to plant hormones. Two plant hormones, strigolactone and methyl jasmonate, produce unique transcript profiles in yeast, affecting phosphate and sugar metabolism, respectively. Genetic analysis in combination with structural studies suggests that SLs require the high-affinity transporter Pho84 to modulate phosphate homeostasis. The ability to study small-molecule plant hormones in a tractable genetic system should have utility in understanding fungal-plant interactions.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"58 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360654","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

Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer 硫化氢介导的过硫化作用可调控非小细胞肺癌中的同型半胱氨酸代谢并增强其铁蛋白沉积能力

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-24 DOI: 10.1016/j.molcel.2024.08.035

Hualei Zheng, Huidi Chen, Yunjie Cai, Min Shen, Xilin Li, Yi Han, Xusheng Deng, Hongjie Cao, Junjia Liu, Hao Li, Benchao Liu, Ganlin Li, Xindong Wang, Hui Chen, Jingjing Hou, Shu-Hai Lin, Lili Zong, Yongyou Zhang

{"title":"Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer","authors":"Hualei Zheng, Huidi Chen, Yunjie Cai, Min Shen, Xilin Li, Yi Han, Xusheng Deng, Hongjie Cao, Junjia Liu, Hao Li, Benchao Liu, Ganlin Li, Xindong Wang, Hui Chen, Jingjing Hou, Shu-Hai Lin, Lili Zong, Yongyou Zhang","doi":"10.1016/j.molcel.2024.08.035","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.035","url":null,"abstract":"Hydrogen sulfide (H₂S), a metabolite of the transsulfuration pathway, has been implicated in ferroptosis, a unique form of cell death caused by lipid peroxidation. While the exact mechanisms controlling ferroptosis remain unclear, our study reveals that H₂S sensitizes human non-small cell lung cancer (NSCLC) cells to this process, particularly when cysteine levels are low. Combining H₂S with cystine depletion significantly enhances the effectiveness of ferroptosis-based cancer therapy. Mechanistically, H₂S persulfidates the 195th cysteine on S-adenosyl homocysteine hydrolase (SAHH), reducing its enzymatic activity. This leads to decreased homocysteine levels, subsequently lowering cysteine and glutathione concentrations under cystine depletion conditions. These changes ultimately increase the vulnerability of NSCLC cells to ferroptosis. Our findings establish H₂S as a key regulator of homocysteine metabolism and a critical factor in determining NSCLC cell susceptibility to ferroptosis. These results highlight the potential of H₂S-based therapies to improve the efficacy of ferroptosis-targeted cancer treatments for NSCLC.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"42 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313557","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

Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module 由可分离激酶模块调控的人类转录媒介的结构基础

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-24 DOI: 10.1016/j.molcel.2024.09.001

Ti-Chun Chao, Shin-Fu Chen, Hee Jong Kim, Hui-Chi Tang, Hsiang-Ching Tseng, An Xu, Leon Palao, Subash Khadka, Tao Li, Mo-Fan Huang, Dung-Fang Lee, Kenji Murakami, Thomas G. Boyer, Kuang-Lei Tsai

{"title":"Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module","authors":"Ti-Chun Chao, Shin-Fu Chen, Hee Jong Kim, Hui-Chi Tang, Hsiang-Ching Tseng, An Xu, Leon Palao, Subash Khadka, Tao Li, Mo-Fan Huang, Dung-Fang Lee, Kenji Murakami, Thomas G. Boyer, Kuang-Lei Tsai","doi":"10.1016/j.molcel.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.09.001","url":null,"abstract":"The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"22 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317258","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

Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions 交替翻译起始产生的突触组织者蛋白形式具有不同的定位和功能

IF 16 1区生物学

Molecular Cell Pub Date : 2024-09-23 DOI: 10.1016/j.molcel.2024.08.032

Paul Jongseo Lee, Yu Sun, Alexa R. Soares, Caroline Fai, Marina R. Picciotto, Junjie U. Guo

{"title":"Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions","authors":"Paul Jongseo Lee, Yu Sun, Alexa R. Soares, Caroline Fai, Marina R. Picciotto, Junjie U. Guo","doi":"10.1016/j.molcel.2024.08.032","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.032","url":null,"abstract":"While many mRNAs contain more than one translation initiation site (TIS), the functions of most alternative TISs and their corresponding protein isoforms (proteoforms) remain undetermined. Here, we showed that alternative usage of CUG and AUG TISs in neuronal pentraxin receptor (NPR) mRNA produced two proteoforms, of which the ratio was regulated by RNA secondary structure and neuronal activity. Downstream AUG initiation truncated the N-terminal transmembrane domain and produced a secreted NPR proteoform sufficient in promoting synaptic clustering of AMPA-type glutamate receptors. Mutations that altered the ratio of NPR proteoforms reduced AMPA receptors in parvalbumin-positive interneurons and affected learning behaviors in mice. In addition to NPR, upstream AUU-initiated N-terminal extension of C1q-like synaptic organizers anchored these otherwise secreted factors to the membrane. Together, these results uncovered the plasticity of N-terminal signal sequences regulated by alternative TIS usage as a potentially widespread mechanism in diversifying protein localization and functions.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"21 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276838","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