Nature Cell Biology最新文献_第2页

SERRATE drives phase separation behaviours to regulate m6A modification and miRNA biogenesis SERRATE 驱动相分离行为以调控 m6A 修饰和 miRNA 生物发生

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-29 DOI: 10.1038/s41556-024-01530-8

Songxiao Zhong, Xindi Li, Changhao Li, Haiyan Bai, Jingjing Chen, Lu Gan, Jiyun Zhu, Taerin Oh, Xingxing Yan, Jiaying Zhu, Niankui Li, Hisashi Koiwa, Thomas Meek, Xu Peng, Bin Yu, Zhonghui Zhang, Xiuren Zhang

{"title":"SERRATE drives phase separation behaviours to regulate m6A modification and miRNA biogenesis","authors":"Songxiao Zhong, Xindi Li, Changhao Li, Haiyan Bai, Jingjing Chen, Lu Gan, Jiyun Zhu, Taerin Oh, Xingxing Yan, Jiaying Zhu, Niankui Li, Hisashi Koiwa, Thomas Meek, Xu Peng, Bin Yu, Zhonghui Zhang, Xiuren Zhang","doi":"10.1038/s41556-024-01530-8","DOIUrl":"https://doi.org/10.1038/s41556-024-01530-8","url":null,"abstract":"The methyltransferase complex (MTC) deposits N6-adenosine (m6A) onto RNA, whereas the microprocessor produces microRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B tends to form insoluble condensates with poor activity, with its level monitored by the 20S proteasome. Conversely, the microprocessor component SERRATE (SE) forms liquid-like condensates, which in turn promote the solubility and stability of the MTC subunit B, leading to increased MTC activity. Consistently, the hypomorphic lines expressing SE variants, defective in MTC interaction or liquid-like phase behaviour, exhibit reduced m6A levels. Reciprocally, MTC can recruit the microprocessor to the MIRNA loci, prompting co-transcriptional cleavage of primary miRNA substrates. Additionally, primary miRNA substrates carrying m6A modifications at their single-stranded basal regions are enriched by m6A readers, which retain the microprocessor in the nucleoplasm for continuing processing. This reveals an unappreciated mechanism of phase separation in RNA modification and processing through MTC and microprocessor coordination.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520170","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

Differential stiffness between brain vasculature and parenchyma promotes metastatic infiltration through vessel co-option 脑血管和脑实质之间的硬度差异通过血管共用促进转移浸润

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-24 DOI: 10.1038/s41556-024-01532-6

Marina Uroz, Amy E. Stoddard, Bryan P. Sutherland, Olivia Courbot, Roger Oria, Linqing Li, Cara R. Ravasio, Mai T. Ngo, Jinling Yang, Juliann B. Tefft, Jeroen Eyckmans, Xue Han, Alberto Elosegui-Artola, Valerie M. Weaver, Christopher S. Chen

{"title":"Differential stiffness between brain vasculature and parenchyma promotes metastatic infiltration through vessel co-option","authors":"Marina Uroz, Amy E. Stoddard, Bryan P. Sutherland, Olivia Courbot, Roger Oria, Linqing Li, Cara R. Ravasio, Mai T. Ngo, Jinling Yang, Juliann B. Tefft, Jeroen Eyckmans, Xue Han, Alberto Elosegui-Artola, Valerie M. Weaver, Christopher S. Chen","doi":"10.1038/s41556-024-01532-6","DOIUrl":"https://doi.org/10.1038/s41556-024-01532-6","url":null,"abstract":"In brain metastasis, cancer cells remain in close contact with the existing vasculature and can use vessels as migratory paths—a process known as vessel co-option. However, the mechanisms regulating this form of migration are poorly understood. Here we use ex vivo brain slices and an organotypic in vitro model for vessel co-option to show that cancer cell invasion along brain vasculature is driven by the difference in stiffness between vessels and the brain parenchyma. Imaging analysis indicated that cells move along the basal surface of vessels by adhering to the basement membrane extracellular matrix. We further show that vessel co-option is enhanced by both the stiffness of brain vasculature, which reinforces focal adhesions through a talin-dependent mechanism, and the softness of the surrounding environment that permits cellular movement. Our work reveals a mechanosensing mechanism that guides cell migration in response to the tissue’s intrinsic mechanical heterogeneity, with implications in cancer invasion and metastasis.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488429","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

Real-time and programmable transcriptome sequencing with PROFIT-seq 利用 PROFIT-seq 进行实时和可编程转录组测序

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-23 DOI: 10.1038/s41556-024-01537-1

Jinyang Zhang, Lingling Hou, Lianjun Ma, Zhengyi Cai, Shujun Ye, Yang Liu, Peifeng Ji, Zhenqiang Zuo, Fangqing Zhao

{"title":"Real-time and programmable transcriptome sequencing with PROFIT-seq","authors":"Jinyang Zhang, Lingling Hou, Lianjun Ma, Zhengyi Cai, Shujun Ye, Yang Liu, Peifeng Ji, Zhenqiang Zuo, Fangqing Zhao","doi":"10.1038/s41556-024-01537-1","DOIUrl":"https://doi.org/10.1038/s41556-024-01537-1","url":null,"abstract":"The high diversity and complexity of the eukaryotic transcriptome make it difficult to effectively detect specific transcripts of interest. Current targeted RNA sequencing methods often require complex pre-sequencing enrichment steps, which can compromise the comprehensive characterization of the entire transcriptome. Here we describe programmable full-length isoform transcriptome sequencing (PROFIT-seq), a method that enriches target transcripts while maintaining unbiased quantification of the whole transcriptome. PROFIT-seq employs combinatorial reverse transcription to capture polyadenylated, non-polyadenylated and circular RNAs, coupled with a programmable control system that selectively enriches target transcripts during sequencing. This approach achieves over 3-fold increase in effective data yield and reduces the time required for detecting specific pathogens or key mutations by 75%. We applied PROFIT-seq to study colorectal polyp development, revealing the intricate relationship between host immune responses and bacterial infection. PROFIT-seq offers a powerful tool for accurate and efficient sequencing of target transcripts while preserving overall transcriptome quantification, with broad applications in clinical diagnostics and targeted enrichment scenarios.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487090","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

Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces 线粒体机械传导通过 MIEF1 协调核对力的反应

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-21 DOI: 10.1038/s41556-024-01527-3

Patrizia Romani, Giada Benedetti, Martina Cusan, Mattia Arboit, Carmine Cirillo, Xi Wu, Georgia Rouni, Vassiliki Kostourou, Mariaceleste Aragona, Costanza Giampietro, Paolo Grumati, Graziano Martello, Sirio Dupont

{"title":"Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces","authors":"Patrizia Romani, Giada Benedetti, Martina Cusan, Mattia Arboit, Carmine Cirillo, Xi Wu, Georgia Rouni, Vassiliki Kostourou, Mariaceleste Aragona, Costanza Giampietro, Paolo Grumati, Graziano Martello, Sirio Dupont","doi":"10.1038/s41556-024-01527-3","DOIUrl":"https://doi.org/10.1038/s41556-024-01527-3","url":null,"abstract":"Tissue-scale architecture and mechanical properties instruct cell behaviour under physiological and diseased conditions, but our understanding of the underlying mechanisms remains fragmentary. Here we show that extracellular matrix stiffness, spatial confinements and applied forces, including stretching of mouse skin, regulate mitochondrial dynamics. Actomyosin tension promotes the phosphorylation of mitochondrial elongation factor 1 (MIEF1), limiting the recruitment of dynamin-related protein 1 (DRP1) at mitochondria, as well as peri-mitochondrial F-actin formation and mitochondrial fission. Strikingly, mitochondrial fission is also a general mechanotransduction mechanism. Indeed, we found that DRP1- and MIEF1/2-dependent fission is required and sufficient to regulate three transcription factors of broad relevance—YAP/TAZ, SREBP1/2 and NRF2—to control cell proliferation, lipogenesis, antioxidant metabolism, chemotherapy resistance and adipocyte differentiation in response to mechanical cues. This extends to the mouse liver, where DRP1 regulates hepatocyte proliferation and identity—hallmark YAP-dependent phenotypes. We propose that mitochondria fulfil a unifying signalling function by which the mechanical tissue microenvironment coordinates complementary cell functions.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451820","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

Ex vivo imaging reveals the spatiotemporal control of ovulation 体外成像揭示排卵的时空控制

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-16 DOI: 10.1038/s41556-024-01524-6

Christopher Thomas, Tabea Lilian Marx, Sarah Mae Penir, Melina Schuh

引用次数: 0

Waste management and cell death in T cells T 细胞中的废物管理和细胞死亡

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-16 DOI: 10.1038/s41556-024-01538-0

Douglas R. Green

引用次数: 0

Now it’s getting bloody in cardiac organoids 现在，它在心脏器官组织中变得鲜血淋漓