Genes & development最新文献

Keratin filaments and soluble vimentin interact with isoform specificity to organize cell signaling. 角蛋白丝和可溶性蛋白与异构体特异性相互作用，组织细胞信号传导。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-09 DOI: 10.1101/gad.353967.126

Surbhi Chouhan, Rajaa Boujemaa-Paterski, Sabahat Munawar, Kushal Bhatt, Laura German Do Nascimiento, Allen Li, Seweryn Gałecki, Divya Rajendran, Tadamoto Isogai, Kevin M Dean, Gaudenz Danuser, Ohad Medalia, Benjamin A Nanes

{"title":"Keratin filaments and soluble vimentin interact with isoform specificity to organize cell signaling.","authors":"Surbhi Chouhan, Rajaa Boujemaa-Paterski, Sabahat Munawar, Kushal Bhatt, Laura German Do Nascimiento, Allen Li, Seweryn Gałecki, Divya Rajendran, Tadamoto Isogai, Kevin M Dean, Gaudenz Danuser, Ohad Medalia, Benjamin A Nanes","doi":"10.1101/gad.353967.126","DOIUrl":"10.1101/gad.353967.126","url":null,"abstract":"The keratin intermediate filament (IF) cytoskeleton provides mechanical support to load-bearing epithelial cells, but its composition varies depending on cell type and tissue context. This variation, the large size of the keratin protein family, and emerging noncanonical functions of individual keratins suggest that the keratin cytoskeleton may have additional, more complicated roles. We report a surprising interaction between the keratin IF cytoskeleton in epithelial cells and soluble oligomers of vimentin, the principal IF component in mesenchymal cells. Rather than forming a cytoskeletal network, soluble vimentin functions as a recruitment factor, organizing regulatory kinases and nonmuscle myosin on keratin filaments to promote signaling. Soluble vimentin and keratin filaments interact through the intrinsically disordered head domain of each protein. Because vimentin preferentially interacts with keratin 6A-containing filaments, increasing keratin 6A expression, as occurs during skin wound healing and cancer development, triggers this myosin-activating signaling cascade. These results demonstrate how varying composition, soluble pools, and client-scaffold interactions through intrinsically disordered regions allow IFs to organize cellular signals in parallel to their canonical mechanical role, supporting context-dependent cell and tissue regulation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C. elegans CEH-43/DLX drives convergent astrocyte differentiation by sequential control of axon guidance and synaptic gene expression programs 秀丽隐杆线虫CEH-43/DLX通过顺序控制轴突引导和突触基因表达程序驱动趋同星形胶质细胞分化

IF 10.5 1区生物学

Genes & development Pub Date : 2026-10-02 DOI: 10.1101/gad.353618.125

Simin Liu,Yoon A. Kim,Ana Milosevic,Nikolaos Stefanakis,Rachel M.J. Craig,Kenneth Bradley,Jinghong J. Tang,Shai Shaham

{"title":"C. elegans\u0000 CEH-43/DLX drives convergent astrocyte differentiation by sequential control of axon guidance and synaptic gene expression programs","authors":"Simin Liu,Yoon A. Kim,Ana Milosevic,Nikolaos Stefanakis,Rachel M.J. Craig,Kenneth Bradley,Jinghong J. Tang,Shai Shaham","doi":"10.1101/gad.353618.125","DOIUrl":"https://doi.org/10.1101/gad.353618.125","url":null,"abstract":"Mammalian radial glia can remodel into astrocytes, which acquire common transcriptional identities despite arising from spatially and lineally distinct progenitors. The molecular mechanisms underlying convergent radial glia-to-astrocyte transformation are not fully understood. To identify regulators of this process, we investigated the development of Caenorhabditis elegans CEPsh glia, astrocyte-like glial cells that arise through remodeling of radial glia-like precursors from distinct progenitor lineages. Using lineage-restricted single-cell RNA sequencing, we characterized a temporally resolved transcriptional program underlying CEPsh glia development. We found that transcriptionally disparate nascent CEPsh glia rapidly converge onto a shared radial glia-like state that promotes nerve ring (brain) assembly, before undergoing progressive, cell division-independent maturation into astrocyte-like glia. We identify the distal-less transcription factor CEH-43 as a key regulator of both developmental phases. CEH-43 directly controls the expression of embryonic genes involved in axon guidance as well as postembryonic genes required for mature glial functions. Comparative transcriptomic and histological analyses reveal conserved molecular features between C. elegans CEPsh glia and mammalian astrocytes, including astrocytic expression of the CEH-43 homolog DLX1. Together, our findings uncover a transcriptional program governing convergent CEPsh glia differentiation and maturation and suggest that core mechanisms of astrocyte development may be evolutionarily conserved.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"40 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090463","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

Dopaminergic transmissive dormancy as a protective state against cellular stress 多巴胺能传递性休眠作为细胞应激的保护状态

IF 10.5 1区生物学

Genes & development Pub Date : 2026-10-02 DOI: 10.1101/gad.353957.126

Kielen R. Zuurbier,Rene Solano Fonseca,Jeffrey Snowden,Peter M. Douglas

引用次数: 0

Differential control of both cell cycle-regulated and quantitative histone mRNA expression by Drosophila Mute. 沉默果蝇对细胞周期调控和定量组蛋白mRNA表达的差异控制。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.353837.126

Mark S Geisler, James P Kemp, Christina A Hill, William F Marzluff, Robert J Duronio

引用次数: 0

Dangerous liaisons: interactions between cancer cells and adipocytes as drivers of cancer progression. 危险的联系：癌细胞和脂肪细胞之间的相互作用作为癌症进展的驱动因素。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.353813.126

Carolina Dehesa Caballero, Almut Schulze

{"title":"Dangerous liaisons: interactions between cancer cells and adipocytes as drivers of cancer progression.","authors":"Carolina Dehesa Caballero, Almut Schulze","doi":"10.1101/gad.353813.126","DOIUrl":"10.1101/gad.353813.126","url":null,"abstract":"Metabolic plasticity and flexibility are key characteristics that allow cancer cells to adapt and thrive in different environments. Specifically, cancer cells can dynamically change the routing of metabolic pathways in response to environmental changes and adapt their metabolic activity depending on local nutrient availability. The tumor microenvironment (TME) plays crucial roles in cancer development and progression. It is now widely accepted that different stromal cells, as well as soluble factors, including metabolites, derived from the TME support cancer cell proliferation and survival and drive migration, invasion, and the formation of metastases. Some cancer types grow in the proximity of adipose tissue (AT), which is mostly composed of mature adipocytes, a specialized cell type responsible for the storage and controlled release of lipids. In response to specific stimuli released by cancer cells, adipocytes can transform into cancer-associated adipocytes (CAAs). CAAs release signaling molecules, and provide fatty acids to cancer cells and other cell types in the TME, which can then utilize these fatty acids as fuel. The interaction between cancer cells and adipocytes creates a dynamic cross-talk that promotes disease progression through multiple mechanisms. In this review, we aim to provide an overview of the main factors in the CAA-cancer cell cross-talk, with a focus on the metabolic consequences of this interaction.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"1598-1613"},"PeriodicalIF":7.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919364","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

Nuclear type I myosins actively support nucleolar and nuclear structure and function. 核I型肌球蛋白积极支持核仁和细胞核的结构和功能。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.353885.126

Audrey Yi Tyan Peng, Jianhui Li, Brian C Freeman

{"title":"Nuclear type I myosins actively support nucleolar and nuclear structure and function.","authors":"Audrey Yi Tyan Peng, Jianhui Li, Brian C Freeman","doi":"10.1101/gad.353885.126","DOIUrl":"10.1101/gad.353885.126","url":null,"abstract":"A nucleus is a remarkably arranged organelle partitioned from the cytosol by a nuclear envelope to encapsulate a highly structured space including a well-organized genome and nucleolus. Despite the conservation, our understanding of the molecular mechanisms driving and maintaining nuclear structure are limited. Here, we investigated the influence of myosin motors in the nucleus. Classically, motor proteins are known for mediating the active transport of cargo facilitating cytoplasmic organization yet how the spacing of nucleoplasmic biomolecules is coordinated was not well defined. We found that nuclear type I myosins were essential for cell division whereas nuclear type II and V myosins were not. Depletion of type I myosin from the nucleus triggered 3D genome disorganization, gene expression changes, nucleolar disruption, and nuclear envelope morphology disfigurement. Declined nucleolar function, including rRNA synthesis and processing, occurred first followed by disorganization of the genome. Notably, nuclear depletion of type I myosin correlated with altered dynamic mobilities of the nucleolar Nop1 (fibrillarin) protein and RNA polymerase I. Overall, nuclear type I myosin is critical for the shape and activities of the nucleolus and nucleus.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"1765-1780"},"PeriodicalIF":7.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684234","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

Temporal gating dictates stress-induced transcript export from the nucleus. 时间门控决定了应激诱导的转录物从细胞核输出。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.353896.126

Noah S Helton, Benjamin Dodd, Stephanie L Moon

{"title":"Temporal gating dictates stress-induced transcript export from the nucleus.","authors":"Noah S Helton, Benjamin Dodd, Stephanie L Moon","doi":"10.1101/gad.353896.126","DOIUrl":"10.1101/gad.353896.126","url":null,"abstract":"Prior studies have largely focused on transcriptional and translational control during stress, but how regulated nuclear mRNA export contributes to the stress response remains unresolved. We show that nuclear mRNA export is progressively inhibited during arsenite and heat stress in human cells. In contrast to previous work largely in yeast that suggests nuclear export of stress-induced transcripts is prioritized through sequence-specific mechanisms, we found that mRNA export is governed by temporal gating, in which the timing of mRNA biogenesis determines the nucleocytoplasmic distribution of mRNAs during stress. Using single-molecule mRNA imaging and transcriptome-wide analyses, we observe the majority of stress-induced mRNAs, including heat shock protein transcripts, accumulate in the nucleus during stress. However, a subset of stress-induced mRNAs, notably HMOX1, JUN, and FOS, escape nuclear retention. mRNAs transcribed early during stress, including those encoding immediate early genes, redox mediators, and protein chaperones, are exported from the nucleus prior to the global inhibition of mRNA export. In contrast, mRNAs transcribed later are retained in the nucleus until stress is resolved. Reporter RNA assays confirm that transcriptional timing determines mRNA export competence. This work reveals that the timing of mRNA production, rather than transcript-specific sequence features, is the major determinant of nuclear export efficiency of stress-induced transcripts in human cells.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"1724-1746"},"PeriodicalIF":7.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human PIF1 clears secondary DNA structures by coupled DNA unwinding and rewinding activities. 人类PIF1通过偶联DNA解绕和复绕活动清除二级DNA结构。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.353775.126

Akshay Jayachandran, Martin Mütze, Kostiantyn Romaniuk, Jessica J R Hudson, Maria Rosaria Dello Stritto, Raphaël Guérois, Ananya Acharya, Stefan Braunshier, Giordano Reginato, Issam Senoussi, Ulrich Rass, Ralf Seidel, Petr Cejka

{"title":"Human PIF1 clears secondary DNA structures by coupled DNA unwinding and rewinding activities.","authors":"Akshay Jayachandran, Martin Mütze, Kostiantyn Romaniuk, Jessica J R Hudson, Maria Rosaria Dello Stritto, Raphaël Guérois, Ananya Acharya, Stefan Braunshier, Giordano Reginato, Issam Senoussi, Ulrich Rass, Ralf Seidel, Petr Cejka","doi":"10.1101/gad.353775.126","DOIUrl":"10.1101/gad.353775.126","url":null,"abstract":"PIF1 family helicases promote genome stability during DNA replication and repair, yet the biochemical activity of human PIF1 (hPIF1) remains poorly understood. Here, we directly compare full-length hPIF1 and budding yeast Pif1 (yPif1) and show that the two enzymes operate differently. In bulk assays, hPIF1 displays weak net DNA unwinding because its robust intrinsic single-stranded DNA (ssDNA) annealing activity rapidly reforms duplex DNA behind the helicase motor. Single-molecule magnetic tweezers experiments reveal that hPIF1 is only modestly slower than yPif1 and similarly processive, indicating that poor apparent unwinding primarily reflects rapid reannealing rather than impaired motor activity. Mutagenesis and structural modeling indicate that this functional divergence depends on a yeast-specific insertion within the catalytic domain. Unlike yPif1, hPIF1 fails to stimulate Polδ-dependent displacement-loop (D-loop) extension, arguing that it does not promote DNA unwinding ahead of the migrating bubble. However, similarly to yPif1, hPIF1 likely unwinds newly synthesized DNA coupled with DNA reannealing behind the migrating D-loop. hPIF1 efficiently remodels intramolecular G-quadruplex DNA into fully base-paired dsDNA, whereas yPif1 generates ssDNA products. Together, our data support a model in which hPIF1 acts primarily as a DNA translocase that couples local unwinding with rapid rewinding to clear secondary DNA structures without generating extensive ssDNA.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"1747-1764"},"PeriodicalIF":7.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706168","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

rRNA 5'ETS processing contributes to nucleolar organization and nuclear architecture. rRNA 5'ETS加工有助于核仁组织和核结构。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.353963.126

Maria Saraí Mendoza-Figueroa, Ellen Lavorando, Yulia Gonskikh, Heidi Elashal, Anthony Yulin Chen, Dawn Carone, Kathy Fange Liu

{"title":"rRNA 5'ETS processing contributes to nucleolar organization and nuclear architecture.","authors":"Maria Saraí Mendoza-Figueroa, Ellen Lavorando, Yulia Gonskikh, Heidi Elashal, Anthony Yulin Chen, Dawn Carone, Kathy Fange Liu","doi":"10.1101/gad.353963.126","DOIUrl":"10.1101/gad.353963.126","url":null,"abstract":"The eukaryotic nucleolus is a highly organized, multilayered structure essential for ribosomal RNA (rRNA) processing and ribosome assembly. While rRNA transcription is known to drive nucleolar assembly, the contribution of downstream processing steps to nucleolar organization remains less well defined. Here, we show that disruption of endonucleolytic cleavage of the 5' external transcribed spacer (5'ETS), a key early step mediated by the SSU processome, leads to pronounced changes in nucleolar structure and organization. These altered nucleoli display reduced dynamic exchange behavior consistent with altered material properties and exhibit changes in the NPM1-associated nucleolar interactome. In parallel, we observe redistribution of heterochromatin markers, indicating broader effects on nuclear organization. Together, our findings support a model in which progression of pre-rRNA processing contributes to maintaining nucleolar compartmentalization and links early steps of ribosome biogenesis to nuclear organization. The nucleolus is a defining feature of eukaryotic cells, yet the principles that maintain its multilayered organization remain incompletely understood. While rRNA transcription is known to initiate nucleolar assembly, we show that a specific downstream processing step, the cleavage of the 5' external transcribed spacer (5'ETS), plays a key role in maintaining nucleolar organization. By functionally uncoupling rRNA transcription from processing, we demonstrate that defects in 5'ETS maturation are associated with alteration of the NPM1-associated interactome and changes in nucleolar dynamics. These findings support a model in which the progression of rRNA processing contributes to the material organization of the nucleolus, linking enzymatic steps in ribosome biogenesis to nuclear architecture.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"1614-1628"},"PeriodicalIF":7.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712044","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

Cycling off: a novel mechanism for differential cell cycle-dependent histone gene expression. 循环关闭：差异细胞周期依赖组蛋白基因表达的新机制。

IF 7.4 1区生物学

Genes & development Pub Date : 2026-10-01 DOI: 10.1101/gad.354085.126

Lauren J Hodkinson, Erica N Larschan

引用次数: 0