Molecular Cell最新文献_第10页

Rho-dependent transcriptional switches regulate the bacterial response to cold shock Rho 依赖性转录开关调控细菌对冷休克的反应

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.07.034

Mildred Delaleau, Nara Figueroa-Bossi, Thuy Duong Do, Patricia Kerboriou, Eric Eveno, Lionello Bossi, Marc Boudvillain

{"title":"Rho-dependent transcriptional switches regulate the bacterial response to cold shock","authors":"Mildred Delaleau, Nara Figueroa-Bossi, Thuy Duong Do, Patricia Kerboriou, Eric Eveno, Lionello Bossi, Marc Boudvillain","doi":"10.1016/j.molcel.2024.07.034","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.034","url":null,"abstract":"Binding of the bacterial Rho helicase to nascent transcripts triggers Rho-dependent transcription termination (RDTT) in response to cellular signals that modulate mRNA structure and accessibility of Rho utilization (Rut) sites. Despite the impact of temperature on RNA structure, RDTT was never linked to the bacterial response to temperature shifts. We show that Rho is a central player in the cold-shock response (CSR), challenging the current view that CSR is primarily a posttranscriptional program. We identify Rut sites in 5′-untranslated regions of key CSR genes/operons (cspA, cspB, cspG, and nsrR-rnr-yjfHI) that trigger premature RDTT at 37°C but not at 15°C. High concentrations of RNA chaperone CspA or nucleotide changes in the cspA mRNA leader reduce RDTT efficiency, revealing how RNA restructuring directs Rho to activate CSR genes during the cold shock and to silence them during cold acclimation. These findings establish a paradigm for how RNA thermosensors can modulate gene expression.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023121","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

Navigating the complexity of Polycomb repression: Enzymatic cores and regulatory modules 探索多聚酶抑制的复杂性：酶核心和调控模块

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.07.030

Simone Tamburri, Samantha Rustichelli, Simona Amato, Diego Pasini

{"title":"Navigating the complexity of Polycomb repression: Enzymatic cores and regulatory modules","authors":"Simone Tamburri, Samantha Rustichelli, Simona Amato, Diego Pasini","doi":"10.1016/j.molcel.2024.07.030","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.030","url":null,"abstract":"Polycomb proteins are a fundamental repressive system that plays crucial developmental roles by orchestrating cell-type-specific transcription programs that govern cell identity. Direct alterations of Polycomb activity are indeed implicated in human pathologies, including developmental disorders and cancer.General Polycomb repression is coordinated by three distinct activities that regulate the deposition of two histone post-translational modifications: tri-methylation of histone H3 lysine 27 (H3K27me3) and histone H2A at lysine 119 (H2AK119ub1). These activities exist in large and heterogeneous multiprotein ensembles consisting of common enzymatic cores regulated by heterogeneous non-catalytic modules composed of a large number of accessory proteins with diverse biochemical properties.Here, we have analyzed the current molecular knowledge, focusing on the functional interaction between the core enzymatic activities and their regulation mediated by distinct accessory modules. This provides a comprehensive analysis of the molecular details that control the establishment and maintenance of Polycomb repression, examining their underlying coordination and highlighting missing information and emerging new features of Polycomb-mediated transcriptional control.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023029","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

snoRNAs in making “snoman” ribosomes 制造 "snooman "核糖体的 snoRNA

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.07.029

Adrianna Dabrowska, Davide Ruggero

引用次数: 0

Mechanism of homology search expansion during recombinational DNA break repair in Saccharomyces cerevisiae 酿酒酵母 DNA 断裂重组修复过程中的同源搜索扩展机制

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.08.003

Agnès Dumont, Nicolas Mendiboure, Jérôme Savocco, Loqmen Anani, Pierrick Moreau, Agnès Thierry, Laurent Modolo, Daniel Jost, Aurèle Piazza

{"title":"Mechanism of homology search expansion during recombinational DNA break repair in Saccharomyces cerevisiae","authors":"Agnès Dumont, Nicolas Mendiboure, Jérôme Savocco, Loqmen Anani, Pierrick Moreau, Agnès Thierry, Laurent Modolo, Daniel Jost, Aurèle Piazza","doi":"10.1016/j.molcel.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.003","url":null,"abstract":"Homology search is a central step of DNA double-strand break (DSB) repair by homologous recombination (HR). How it operates in cells remains elusive. We developed a Hi-C-based methodology to map single-stranded DNA (ssDNA) contacts genome-wide in S. cerevisiae, which revealed two main homology search phases. Initial search conducted by short Rad51-ssDNA nucleoprotein filaments (NPFs) is confined in cis by cohesin-mediated chromatin loop folding. Progressive growth of stiff NPFs enables exploration of distant genomic sites. Long-range resection drives this transition from local to genome-wide search by increasing the probability of assembling extensive NPFs. DSB end-tethering promotes coordinated search by opposite NPFs. Finally, an autonomous genetic element on chromosome III engages the NPF, which stimulates homology search in its vicinity. This work reveals the mechanism of the progressive expansion of homology search that is orchestrated by chromatin organizers, long-range resection, end-tethering, and specialized genetic elements and that exploits the stiff NPF structure conferred by Rad51 oligomerization.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023042","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

A FACT about macroH2A removal in immune gene activation 关于免疫基因激活过程中去除宏 H2A 的事实

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.07.028

Oliver Meers, Marcus Buschbeck

引用次数: 0

Ubiquitin gets sweet: Sugar-mediated ubiquitination regulates Nrf1 function 泛素变甜了糖介导的泛素化调节 Nrf1 的功能

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.07.023

Alison C. Mody, Christina M. Woo

引用次数: 0

RAD51 protects abasic sites to prevent replication fork breakage RAD51 保护消融位点，防止复制叉断裂

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-22 DOI: 10.1016/j.molcel.2024.07.004

Yodhara Wijesekara Hanthi, Miguel Angel Ramirez-Otero, Robert Appleby, Anna De Antoni, Luay Joudeh, Vincenzo Sannino, Salli Waked, Alessandra Ardizzoia, Viviana Barra, Daniele Fachinetti, Luca Pellegrini, Vincenzo Costanzo

{"title":"RAD51 protects abasic sites to prevent replication fork breakage","authors":"Yodhara Wijesekara Hanthi, Miguel Angel Ramirez-Otero, Robert Appleby, Anna De Antoni, Luay Joudeh, Vincenzo Sannino, Salli Waked, Alessandra Ardizzoia, Viviana Barra, Daniele Fachinetti, Luca Pellegrini, Vincenzo Costanzo","doi":"10.1016/j.molcel.2024.07.004","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.004","url":null,"abstract":"Abasic sites are DNA lesions repaired by base excision repair. Cleavage of unrepaired abasic sites in single-stranded DNA (ssDNA) can lead to chromosomal breakage during DNA replication. How rupture of abasic DNA is prevented remains poorly understood. Here, using cryoelectron microscopy (cryo-EM), Xenopus laevis egg extracts, and human cells, we show that RAD51 nucleofilaments specifically recognize and protect abasic sites, which increase RAD51 association rate to DNA. In the absence of BRCA2 or RAD51, abasic sites accumulate as a result of DNA base methylation, oxidation, and deamination, inducing abasic ssDNA gaps that make replicating DNA fibers sensitive to APE1. RAD51 assembled on abasic DNA prevents abasic site cleavage by the MRE11-RAD50 complex, suppressing replication fork breakage triggered by an excess of abasic sites or POLθ polymerase inhibition. Our study highlights the critical role of BRCA2 and RAD51 in safeguarding against unrepaired abasic sites in DNA templates stemming from base alterations, ensuring genomic stability.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023089","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

Proteasome resides in and dismantles plant heat stress granules constitutively 蛋白酶体连续驻留在植物热胁迫颗粒中并将其分解

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-21 DOI: 10.1016/j.molcel.2024.07.033

Zhouli Xie, Shuai Zhao, Yuchen Tu, Enhui Liu, Ying Li, Xingwei Wang, Changtian Chen, Shuwei Zhai, Jie Qi, Chengyun Wu, Honghong Wu, Mian Zhou, Wei Wang

{"title":"Proteasome resides in and dismantles plant heat stress granules constitutively","authors":"Zhouli Xie, Shuai Zhao, Yuchen Tu, Enhui Liu, Ying Li, Xingwei Wang, Changtian Chen, Shuwei Zhai, Jie Qi, Chengyun Wu, Honghong Wu, Mian Zhou, Wei Wang","doi":"10.1016/j.molcel.2024.07.033","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.033","url":null,"abstract":"Stress granules (SGs) are conserved reversible cytoplasmic condensates enriched with aggregation-prone proteins assembled in response to various stresses. How plants regulate SG dynamics is unclear. Here, we show that 26S proteasome is a stable component of SGs, promoting the overall clearance of SGs without affecting the molecular mobility of SG components. Increase in either temperature or duration of heat stress reduces the molecular mobility of SG marker proteins and suppresses SG clearance. Heat stress induces dramatic ubiquitylation of SG components and enhances the activities of SG-resident proteasomes, allowing the degradation of SG components even during the assembly phase. Their proteolytic activities enable the timely disassembly of SGs and secure the survival of plant cells during the recovery from heat stress. Therefore, our findings identify the cellular process that de-couples macroscopic dynamics of SGs from the molecular dynamics of its constituents and highlights the significance of the proteasomes in SG disassembly.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023091","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

RNA interacts with topoisomerase I to adjust DNA topology RNA 与拓扑异构酶 I 相互作用，调整 DNA 拓扑结构

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-21 DOI: 10.1016/j.molcel.2024.07.032

Mannan Bhola, Kouki Abe, Paola Orozco, Homa Rahnamoun, Pedro Avila-Lopez, Elijah Taylor, Nefertiti Muhammad, Bei Liu, Prachi Patel, John F. Marko, Anne C. Starner, Chuan He, Eric L. Van Nostrand, Alfonso Mondragón, Shannon M. Lauberth

{"title":"RNA interacts with topoisomerase I to adjust DNA topology","authors":"Mannan Bhola, Kouki Abe, Paola Orozco, Homa Rahnamoun, Pedro Avila-Lopez, Elijah Taylor, Nefertiti Muhammad, Bei Liu, Prachi Patel, John F. Marko, Anne C. Starner, Chuan He, Eric L. Van Nostrand, Alfonso Mondragón, Shannon M. Lauberth","doi":"10.1016/j.molcel.2024.07.032","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.032","url":null,"abstract":"Topoisomerase I (TOP1) is an essential enzyme that relaxes DNA to prevent and dissipate torsional stress during transcription. However, the mechanisms underlying the regulation of TOP1 activity remain elusive. Using enhanced cross-linking and immunoprecipitation (eCLIP) and ultraviolet-cross-linked RNA immunoprecipitation followed by total RNA sequencing (UV-RIP-seq) in human colon cancer cells along with RNA electrophoretic mobility shift assays (EMSAs), biolayer interferometry (BLI), and in vitro RNA-binding assays, we identify TOP1 as an RNA-binding protein (RBP). We show that TOP1 directly binds RNA in vitro and in cells and that most RNAs bound by TOP1 are mRNAs. Using a TOP1 RNA-binding mutant and topoisomerase cleavage complex sequencing (TOP1cc-seq) to map TOP1 catalytic activity, we reveal that RNA opposes TOP1 activity as RNA polymerase II (RNAPII) commences transcription of active genes. We further demonstrate the inhibitory role of RNA in regulating TOP1 activity by employing DNA supercoiling assays and magnetic tweezers. These findings provide insight into the coordinated actions of RNA and TOP1 in regulating DNA topological stress intrinsic to RNAPII-dependent transcription.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023084","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

Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins 整体插入酶复合物在生物物理多样性ER膜蛋白的生物生成过程中的作用

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-21 DOI: 10.1016/j.molcel.2024.08.005

Katharine R. Page, Vy N. Nguyen, Tino Pleiner, Giovani Pinton Tomaleri, Maxine L. Wang, Alina Guna, Masami Hazu, Ting-Yu Wang, Tsui-Fen Chou, Rebecca M. Voorhees

{"title":"Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins","authors":"Katharine R. Page, Vy N. Nguyen, Tino Pleiner, Giovani Pinton Tomaleri, Maxine L. Wang, Alina Guna, Masami Hazu, Ting-Yu Wang, Tsui-Fen Chou, Rebecca M. Voorhees","doi":"10.1016/j.molcel.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.08.005","url":null,"abstract":"Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein-coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC. We found that the back of Sec61 (BOS) complex, a component of the multipass translocon, was a physical and genetic interactor of the EMC. Functional and structural analysis of the EMC⋅BOS holocomplex showed that characteristics of a GPCR’s soluble domain determine its biogenesis pathway. In contrast to prevailing models, no single insertase handles all substrates. We instead propose a unifying model for coordination between the EMC, the multipass translocon, and Sec61 for the biogenesis of diverse membrane proteins in human cells.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023030","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