Molecular Cell最新文献

Global translational regulation by Prkra: Is PKR no longer needed? PKR的全球翻译调控：是否不再需要PKR ？

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.016

Mihye Lee, Jaemin Jeon, Yoosik Kim

引用次数: 0

Molecular arms in microbial defense: Argonautes and Cas4 nucleases team up 微生物防御中的分子臂：Argonautes和Cas4核酸酶合作

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.024

Sucharita Sarkar, Ian J. MacRae

引用次数: 0

Proteasome: An antibiotic arsenal in anti-bacterial innate immunity 蛋白酶体：抗细菌先天免疫中的一个抗生素库

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.025

Yi Zheng, Chengjiang Gao

引用次数: 0

U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation U1 snRNP通过抑制过早聚腺苷酸化调节替代启动子活性

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.021

GyeungYun Kim, Christine L. Carroll, Zachary Peters Wakefield, Mustafa Tuncay, Ana Fiszbein

{"title":"U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation","authors":"GyeungYun Kim, Christine L. Carroll, Zachary Peters Wakefield, Mustafa Tuncay, Ana Fiszbein","doi":"10.1016/j.molcel.2025.04.021","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.04.021","url":null,"abstract":"Emerging evidence indicates that splicing factors mediate the close link between transcription and splicing. However, the mechanisms underlying this coupling remain unclear. U1 small nuclear ribonucleoprotein particle (U1 snRNP) not only initiates splicing but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcriptional elongation. Here, we show that U1 snRNP regulates alternative promoter activity in human cells by inhibiting premature polyadenylation. In genes carrying premature polyadenylation sites between two promoters, U1 snRNP inhibition with antisense oligonucleotides leads to a significant decrease in downstream promoter activity. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility, decreased RNA polymerase II serine 5 phosphorylation, and increased promoter-proximal pause at downstream promoters. Our findings support a model in which U1 snRNP favors productive elongation from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"28 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980016","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

Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay 核糖体通过广义移码和框外mRNA衰变调节转录组丰度

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.022

Yujie Zhang, Lilit Nersisyan, Eliska Fürst, Ioannis Alexopoulos, Carlos Santolaria, Susanne Huch, Claudio Bassot, Elena Garre, Per Sunnerhagen, Ilaria Piazza, Vicent Pelechano

{"title":"Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay","authors":"Yujie Zhang, Lilit Nersisyan, Eliska Fürst, Ioannis Alexopoulos, Carlos Santolaria, Susanne Huch, Claudio Bassot, Elena Garre, Per Sunnerhagen, Ilaria Piazza, Vicent Pelechano","doi":"10.1016/j.molcel.2025.04.022","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.04.022","url":null,"abstract":"Cells need to adapt their transcriptome to quickly match cellular needs in changing environments. mRNA abundance can be controlled by altering both its synthesis and decay. Here, we show how, in response to poor nutritional conditions, the bulk of the <em>S. cerevisiae</em> transcriptome undergoes −1 ribosome frameshifts and experiences an accelerated out-of-frame co-translational mRNA decay. Using RNA metabolic labeling, we demonstrate that in poor nutritional conditions, nonsense-mediated mRNA decay (NMD)-dependent degradation represents at least one-third of the total mRNA decay. We further characterize this mechanism and identify low codon optimality as a key factor for ribosomes to induce out-of-frame mRNA decay. Finally, we show that this phenomenon is conserved from bacteria to humans. Our work provides evidence for a direct regulatory feedback mechanism coupling protein demand with the control of mRNA abundance to limit cellular growth and broadens the functional landscape of mRNA quality control.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"141 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980084","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

Quality control of ribosome assembly: Kinetic discrimination at work 核糖体组装的质量控制：工作中的动力学鉴别

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.023

Yunyang Zhang, Ning Gao

引用次数: 0

Regulation of RNA polymerase II transcription through re-initiation and bursting RNA聚合酶II转录的再起始和破裂调控

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.011

Michael Nagel, Dylan J. Taatjes

引用次数: 0

Uracil-induced replication stress drives mutations, genome instability, anti-cancer treatment efficacy, and resistance 尿嘧啶诱导的复制应激驱动突变、基因组不稳定、抗癌治疗效果和耐药性

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-15 DOI: 10.1016/j.molcel.2025.04.015

Oliver Mortusewicz, James Haslam, Helge Gad, Thomas Helleday

引用次数: 0

Structural basis of human CHD1 nucleosome recruitment and pausing 人CHD1核小体募集和暂停的结构基础

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-06 DOI: 10.1016/j.molcel.2025.04.020

Allison M. James, Lucas Farnung

{"title":"Structural basis of human CHD1 nucleosome recruitment and pausing","authors":"Allison M. James, Lucas Farnung","doi":"10.1016/j.molcel.2025.04.020","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.04.020","url":null,"abstract":"Chromatin remodelers regulate gene expression and genome maintenance by controlling nucleosome positioning, but the structural basis for their regulated and directional activity remains poorly understood. Here, we present three cryoelectron microscopy (cryo-EM) structures of human chromodomain helicase DNA-binding protein 1 (CHD1) bound to nucleosomes that reveal previously unobserved recruitment and regulatory states. We identify a structural element, termed the “anchor element,” that connects the CHD1 ATPase motor to the nucleosome entry-side acidic patch. The anchor element coordinates with other regulatory modules, including the gating element, which undergoes a conformational switch critical for remodeling. Our structures demonstrate how the DNA-binding region of CHD1 binds entry- and exit-side DNA during remodeling to achieve directional sliding. The observed structural elements are conserved across chromatin remodelers, suggesting a unified mechanism for nucleosome recognition and remodeling. Our findings show how chromatin remodelers couple nucleosome recruitment to regulated DNA translocation, providing a framework for understanding chromatin remodeler mechanisms beyond DNA translocation.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"99 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910632","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

ZNF574 is a quality control factor for defective ribosome biogenesis intermediates ZNF574是缺陷核糖体生物发生中间体的质量控制因子

IF 16 1区生物学

Molecular Cell Pub Date : 2025-05-05 DOI: 10.1016/j.molcel.2025.04.017

Jared F. Akers, Michael LaScola, Adrian Bothe, Hanna Suh, Carmen Jung, Zachary D. Stolp, Tanushree Ghosh, Liewei L. Yan, Yuming Wang, Michelle Macurak, Amisha Devan, Mary C. McKinney, Tarabryn S. Grismer, Andres V. Reyes, Eric J. Ross, Tianyi Hu, Shou-Ling Xu, Nenad Ban, Kamena K. Kostova

{"title":"ZNF574 is a quality control factor for defective ribosome biogenesis intermediates","authors":"Jared F. Akers, Michael LaScola, Adrian Bothe, Hanna Suh, Carmen Jung, Zachary D. Stolp, Tanushree Ghosh, Liewei L. Yan, Yuming Wang, Michelle Macurak, Amisha Devan, Mary C. McKinney, Tarabryn S. Grismer, Andres V. Reyes, Eric J. Ross, Tianyi Hu, Shou-Ling Xu, Nenad Ban, Kamena K. Kostova","doi":"10.1016/j.molcel.2025.04.017","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.04.017","url":null,"abstract":"Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that participate in numerous interdependent steps. The complexity and essentiality of this process create opportunities for deleterious mutations to occur, accumulate, and impact downstream cellular processes. “Dead-end” ribosome intermediates that result from biogenesis errors are rapidly degraded, affirming the existence of quality control (QC) pathway(s) that monitor ribosome assembly. However, the factors that differentiate between on-path and dead-end intermediates are unknown. We engineered a system to perturb ribosome assembly in human cells and discovered that faulty ribosomes are degraded via the ubiquitin-proteasome system. We identified <em>ZNF574</em> as a key component of a QC pathway, which we term the ribosome assembly surveillance pathway (RASP). In an animal model, loss of ZNF574 leads to developmental defects, emphasizing the importance of RASP in organismal health.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"225 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905432","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