Molecular Cell最新文献_第10页

A tale of two strands: Decoding chromatin replication through strand-specific sequencing 两条链的故事：通过链特异性测序解码染色质复制

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-16 DOI: 10.1016/j.molcel.2024.10.035

Zhiming Li, Zhiguo Zhang

引用次数: 0

Metabolism-driven chromatin dynamics: Molecular principles and technological advances 代谢驱动的染色质动力学：分子原理和技术进步

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-16 DOI: 10.1016/j.molcel.2024.12.012

Varun Sahu, Chao Lu

引用次数: 0

USP4 Auto-Deubiquitylation Promotes Homologous Recombination USP4自去泛素化促进同源重组

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-15 DOI: 10.1016/j.molcel.2024.12.024

Paul Wijnhoven, Rebecca Konietzny, Andrew N. Blackford, Jonathan Travers, Benedikt M. Kessler, Ryotaro Nishi, Stephen P. Jackson

引用次数: 0

Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics 通过高复用成像和深度视觉蛋白质组学解读功能性肿瘤免疫串扰

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-14 DOI: 10.1016/j.molcel.2024.12.023

Xiang Zheng, Andreas Mund, Matthias Mann

{"title":"Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics","authors":"Xiang Zheng, Andreas Mund, Matthias Mann","doi":"10.1016/j.molcel.2024.12.023","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.023","url":null,"abstract":"Deciphering the intricate tumor-immune interactions within the microenvironment is crucial for advancing cancer immunotherapy. Here, we introduce mipDVP, an advanced approach integrating highly multiplexed imaging, single-cell laser microdissection, and sensitive mass spectrometry to spatially profile the proteomes of distinct cell populations in a human colorectal and tonsil cancer with high sensitivity. In a colorectal tumor—a representative cold tumor—we uncovered spatial compartmentalization of an immunosuppressive macrophage barrier that potentially impedes T cell infiltration. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In a tonsil cancer sample—a hot tumor—we identified significant proteomic heterogeneity among cells influenced by proximity to cytotoxic T cell subtypes. T cells in the tumor parenchyma exhibit metabolic adaptations to hypoxic regions. Our spatially resolved, highly multiplexed strategy deciphers the complex cellular interplay within the tumor microenvironment, offering valuable insights for identifying immunotherapy targets and predictive signatures.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"22 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974563","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 5′ splice site recognition by the minor spliceosome 小剪接体识别 5′剪接位点的结构基础

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-14 DOI: 10.1016/j.molcel.2024.12.017

Jiangfeng Zhao, Daniel Peter, Irina Brandina, Xiangyang Liu, Wojciech P. Galej

{"title":"Structural basis of 5′ splice site recognition by the minor spliceosome","authors":"Jiangfeng Zhao, Daniel Peter, Irina Brandina, Xiangyang Liu, Wojciech P. Galej","doi":"10.1016/j.molcel.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.017","url":null,"abstract":"The minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying molecular mechanisms remain elusive. Here, we report a cryoelectron microscopy (cryo-EM) reconstruction of the 13-subunit human U11 small nuclear ribonucleoprotein particle (snRNP) complex in apo and substrate-bound forms, revealing the architecture of the U11 small nuclear RNA (snRNA), five minor spliceosome-specific factors, and the mechanism of the U12-type 5′ splice site (5′SS) recognition. SNRNP25 and SNRNP35 specifically recognize U11 snRNA, while PDCD7 bridges SNRNP25 and SNRNP48, located at the distal ends of the particle. SNRNP48 and ZMAT5 are positioned near the 5′ end of U11 snRNA and stabilize binding of the incoming 5′SS. Recognition of the U12-type 5′SS is achieved through base-pairing to the 5′ end of the U11 snRNA and unexpected, non-canonical base-triple interactions with the U11 snRNA stem-loop 3. Our structures provide mechanistic insights into U12-dependent intron recognition and the evolution of the splicing machinery.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"29 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974550","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

Centromere inactivation during aging can be rescued in human cells 人类细胞在衰老过程中可以挽救着丝粒失活

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-13 DOI: 10.1016/j.molcel.2024.12.018

Sweta Sikder, Songjoon Baek, Truman McNeil, Yamini Dalal

引用次数: 0

RBBP6 anchors pre-mRNA 3′ end processing to nuclear speckles for efficient gene expression RBBP6将前mrna 3 '端加工锚定在核斑点上，以实现有效的基因表达

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-10 DOI: 10.1016/j.molcel.2024.12.016

Yoseop Yoon, Elodie Bournique, Lindsey V. Soles, Hong Yin, Hsu-Feng Chu, Christopher Yin, Yinyin Zhuang, Xiangyang Liu, Liang Liu, Joshua Jeong, Clinton Yu, Marielle Valdez, Lusong Tian, Lan Huang, Xiaoyu Shi, Georg Seelig, Fangyuan Ding, Liang Tong, Rémi Buisson, Yongsheng Shi

{"title":"RBBP6 anchors pre-mRNA 3′ end processing to nuclear speckles for efficient gene expression","authors":"Yoseop Yoon, Elodie Bournique, Lindsey V. Soles, Hong Yin, Hsu-Feng Chu, Christopher Yin, Yinyin Zhuang, Xiangyang Liu, Liang Liu, Joshua Jeong, Clinton Yu, Marielle Valdez, Lusong Tian, Lan Huang, Xiaoyu Shi, Georg Seelig, Fangyuan Ding, Liang Tong, Rémi Buisson, Yongsheng Shi","doi":"10.1016/j.molcel.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.016","url":null,"abstract":"Pre-mRNA 3′ processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3′ processing in human cells. We show that the essential pre-mRNA 3′ processing factor retinoblastoma-binding protein 6 (RBBP6) associates strongly with NSs via its C-terminal intrinsically disordered region (IDR). Importantly, although the conserved N-terminal domain (NTD) of RBBP6 is sufficient for pre-mRNA 3′ processing <em>in vitro</em>, its IDR-mediated association with NSs is required for efficient pre-mRNA 3′ processing in cells. Through proximity labeling analyses, we provide evidence that pre-mRNA 3′ processing for over 50% of genes occurs near NSs. We propose that NSs serve as hubs for RNA polymerase II transcription, pre-mRNA splicing, and 3′ processing, thereby enhancing the efficiency and coordination of different gene expression steps.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"2 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939575","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

Chromatin hubs drive key regulatory networks in leukemia 染色质中心驱动白血病的关键调控网络

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-02 DOI: 10.1016/j.molcel.2024.12.011

Alok Swaroop, Feng Yue

引用次数: 0

Transposon exonization generates new protein-coding sequences 转座子外显子产生新的蛋白质编码序列

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-02 DOI: 10.1016/j.molcel.2024.12.009

Yantao Hong, Xiaohua Shen

引用次数: 0

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription mRNA输出因子将新生转录物存储在核斑点中，作为对瞬时全局转录抑制的适应性反应

IF 16 1区生物学

Molecular Cell Pub Date : 2025-01-02 DOI: 10.1016/j.molcel.2024.12.008

Tobias D. Williams, Ewa M. Michalak, Kirstyn.T. Carey, Enid Y.N. Lam, Ashley Anderson, Esther Griesbach, Yih-Chih Chan, Panagiotis Papasaikas, Vicky W.T. Tan, Linh Ngo, Laura MacPherson, Omer Gilan, Amber Rucinski, Anna Rutkowska-Klute, Nico Zinn, Paola Grandi, Marcus Bantscheff, Rab K. Prinjha, Sarah-Jane Dawson, Jeffrey A. Chao, Mark A. Dawson

{"title":"mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription","authors":"Tobias D. Williams, Ewa M. Michalak, Kirstyn.T. Carey, Enid Y.N. Lam, Ashley Anderson, Esther Griesbach, Yih-Chih Chan, Panagiotis Papasaikas, Vicky W.T. Tan, Linh Ngo, Laura MacPherson, Omer Gilan, Amber Rucinski, Anna Rutkowska-Klute, Nico Zinn, Paola Grandi, Marcus Bantscheff, Rab K. Prinjha, Sarah-Jane Dawson, Jeffrey A. Chao, Mark A. Dawson","doi":"10.1016/j.molcel.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.12.008","url":null,"abstract":"Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export. We demonstrate that retention of newly transcribed mRNA in nuclear speckles is an adaptive response to chemically distinct transcriptional inhibitors. Retained transcripts are fully processed and accumulate in proportion to the expression level of the genes from which they emanate. The TREX mRNA export complex plays an integral role in directing nascent transcripts to nuclear speckles where they are bound to NXF1, protected from degradation, and poised for rapid export following re-initiation of transcription. Our findings provide new insights into the crosstalk between transcription and mRNA export with important implications for drugs aiming to inhibit transcription for therapeutic gain.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"34 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912157","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