G3: Genes|Genomes|Genetics最新文献

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Investigating the role of phosphodiesterase Pde2 in coordinating resource reallocation through the environmental stress response. 研究磷酸二酯酶Pde2通过环境应激反应在协调资源再分配中的作用。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-22 DOI: 10.1093/g3journal/jkag200
Rachel A Kocik, Jamie Ahrens, Audrey P Gasch
{"title":"Investigating the role of phosphodiesterase Pde2 in coordinating resource reallocation through the environmental stress response.","authors":"Rachel A Kocik, Jamie Ahrens, Audrey P Gasch","doi":"10.1093/g3journal/jkag200","DOIUrl":"10.1093/g3journal/jkag200","url":null,"abstract":"<p><p>Yeast responding to acute stress reallocates cellular resources, in part via the environmental stress response (ESR) that induces stress-defense genes while repressing ribosome biogenesis and growth genes. The purpose and regulation of coordinated induction and repression are incompletely understood, but both responses are influenced by ESR transcription factors Msn2 and Msn4 (Msn2/4). Here, we used single-cell microscopy and transcriptomic analysis to investigate the role of the upstream regulator Pde2 in ESR regulation and poststress fitness. Loss of PDE2 weakened and shortened Msn2 activation following salt stress and produced muted induction of Msn2/4 targets, similar to a msn2Δmsn4Δ strain. In contrast, Pde2 had at most a minor impact on the ESR repressor Dot6, yet was important for repression of its targets beyond Msn2/4 influence. Consistent with our recent resource-reallocation model, pde2Δ cells had normal or faster poststress growth rates, despite weaker activation of the ESR. We discuss implications for ESR regulation and function.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The Drosophila FET ortholog Cabeza is an essential cofactor for ETV4-mediated activation of GGAA microsatellite neoenhancers. 果蝇FET同源物Cabeza是etv4介导的GGAA微卫星新增强子激活的重要辅助因子。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-22 DOI: 10.1093/g3journal/jkag265
Cristina Molnar, Jose Reina, Jaume Mora, Cayetano Gonzalez
{"title":"The Drosophila FET ortholog Cabeza is an essential cofactor for ETV4-mediated activation of GGAA microsatellite neoenhancers.","authors":"Cristina Molnar, Jose Reina, Jaume Mora, Cayetano Gonzalez","doi":"10.1093/g3journal/jkag265","DOIUrl":"https://doi.org/10.1093/g3journal/jkag265","url":null,"abstract":"<p><p>The conversion of transcriptionally silent GGAA microsatellites (GGAAµSats) into functional enhancers by FET::ETS oncogenic fusions is a hallmark of Ewing sarcoma. However, emerging evidence implicates non-fused, full-length oncogenic ETS transcription factors in activating these repeats in other malignancies. Evaluating the in vivo transcriptional requirements of various human ETS factors in Drosophila, we found that human ETV4 associates with and robustly activates GGAAµSats in a tissue-specific manner. This activation is strongly inhibited by the human ETS repressor ETV6. Taking advantage of low genetic redundancy in Drosophila, we identified Cabeza (Caz), the single fly FET ortholog, as a necessary cofactor for ETV4-mediated transcription at GGAAµSats. Conversely, EWS::FLI1-mediated transcriptional activation of GGAAµSats is entirely independent of endogenous Caz, highlighting the distinct mechanics of covalent tethering versus non-covalent physical complexes. Collectively, our findings provide in vivo evidence that non-fused ETS factors cooperate with endogenous FET proteins to drive transcription from silent GGAA repeats, mechanistically validating this regulatory transformation known to operate as an oncogenic mechanism beyond Ewing sarcoma.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Evolutionary dynamics of polymorphic endogenous retrovirus insertions across wild house mouse populations. 多态内源性逆转录病毒插入在野生家鼠种群中的进化动力学。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-22 DOI: 10.1093/g3journal/jkag270
Tomoki Yano, Toyoyuki Takada, Kazumichi Fujiwara, Dai Watabe, Shutaro Hirose, Hiroshi Masuya, Toshinori Endo, Naoki Osada
{"title":"Evolutionary dynamics of polymorphic endogenous retrovirus insertions across wild house mouse populations.","authors":"Tomoki Yano, Toyoyuki Takada, Kazumichi Fujiwara, Dai Watabe, Shutaro Hirose, Hiroshi Masuya, Toshinori Endo, Naoki Osada","doi":"10.1093/g3journal/jkag270","DOIUrl":"https://doi.org/10.1093/g3journal/jkag270","url":null,"abstract":"<p><p>Endogenous retroviruses (ERVs) represent a major source of structural variation in mammalian genomes, yet their diversity in wild populations remains poorly understood. Here, we conduct a comprehensive genome-wide survey of non-reference ERV insertions in wild house mice (Mus musculus) to characterize their distribution and evolutionary dynamics. Using a newly developed, computationally efficient bioinformatics pipeline, we detected and annotated over 100,000 non-reference ERV insertions from short-read sequencing data across 163 wild mouse genomes sampled across Eurasia. Our analyses revealed marked differences in ERV insertion patterns among subspecies and populations, including variation in genomic localization and population-specific polymorphisms. These heterogeneous patterns suggest distinct evolutionary histories and host-retrovirus interactions across populations. As a case study, we describe the distribution of the ERV-derived Fv4 gene, which shows subspecies-restricted presence and confers resistance to murine leukemia viruses (MLVs). Several lines of evidence showed that the spread of Fv4 insertions in Korean population has been driven by adaptive introgression from neighboring populations. Our study provides the first large-scale population genomic scan of ERV diversity in wild house mice. By cataloguing extensive polymorphism in non-reference ERV insertions, our results highlight the role of ERVs as dynamic genomic elements that contribute to structural variation and adaptive evolution.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Chromosome-level genome assembly of the Endangered scaly-sided merganser Mergus squamatus with insight into its demographic history. 濒危鳞片面秋沙鸭的染色体水平基因组组装与洞察其人口历史。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-22 DOI: 10.1093/g3journal/jkag268
Joshua J Wright, Heleen De Weerd, Alexander C Lees, Kirsty J Shaw, Sarah M Griffiths
{"title":"Chromosome-level genome assembly of the Endangered scaly-sided merganser Mergus squamatus with insight into its demographic history.","authors":"Joshua J Wright, Heleen De Weerd, Alexander C Lees, Kirsty J Shaw, Sarah M Griffiths","doi":"10.1093/g3journal/jkag268","DOIUrl":"https://doi.org/10.1093/g3journal/jkag268","url":null,"abstract":"<p><p>The scaly-sided merganser, Mergus squamatus, is an Endangered piscivorous duck which has been declining since the late 1900s due to habitat loss, over-hunting, and climate change. Despite being a species of global conservation concern and subject to ex- and in-situ conservation efforts, genomic research has been limited, hindering our understanding of its population genetic status and evolutionary history. In this study, we present the first fully annotated, chromosome-level genome for the scaly-sided merganser, generated using Oxford Nanopore long reads, Illumina short reads, and Hi-C sequencing. The final assembly spans 1.1 Gb across 308 scaffolds, 64 of which are anchored into 35 chromosomes, plus the mitogenome, covering 99.5% of the genome. The assembly shows high contiguity (N50 = 84.3Mb) and completeness, with a Benchmarking Universal Single-Copy Ortholog (BUSCO) score of 98%. Repeat sequences comprise 9.55% of the genome. Homology-based gene annotation identified ∼15,200 protein-coding genes. A complete 16,624 bp mitochondrial genome was also assembled and annotated. Synteny analysis revealed strong chromosomal conservation across the wider Anatidae family, with evidence of lineage-specific rearrangements. Pairwise Sequential Markovian Coalescence modelling indicates recent stability in the effective population size of the species, with past declines coinciding with Pleistocene glacial cycles. Our high-quality genome provides an essential resource for conservation genomic and evolutionary studies of the scaly-sided merganser, supporting ongoing efforts to manage and protect this globally threatened species.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Tenascin N contributes to spinal motor nerve morphogenesis during development. Tenascin N参与脊髓运动神经发育过程中的形态发生。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-21 DOI: 10.1093/g3journal/jkag259
Charles G Marcucci, Brianna Peskin Gifford, Marieke Jones, Coleman Blanton, Sarah Kucenas
{"title":"Tenascin N contributes to spinal motor nerve morphogenesis during development.","authors":"Charles G Marcucci, Brianna Peskin Gifford, Marieke Jones, Coleman Blanton, Sarah Kucenas","doi":"10.1093/g3journal/jkag259","DOIUrl":"10.1093/g3journal/jkag259","url":null,"abstract":"<p><p>Spinal motor nerves are an integral component of the nervous system whose development requires the coordination of many diverse cell types, including motor neurons, glia, and muscle. Although several molecular mechanisms guiding these interactions are known, many remain to be uncovered. Extracellular matrix (ECM) proteins also play a critical role in motor nerve assembly, yet their functions are less understood compared to classical pathfinding and guidance cues. Here, we identify a role for tenascin-n (tnn), an ECM glycoprotein, in spinal motor nerve development in zebrafish. Using in situ hybridization and immunohistochemistry, we show that tnn/Tnn is expressed and localized along vertical myosepta and the border of the ventral neural tube during spinal motor nerve development. To assess its function, we generated a CRISPR/Cas9 mutant allele, tnnuva96, and performed in vivo imaging and morphological analysis throughout motor nerve development. Loss of tnn leads to a subtle and transient trend of increase in ectopic motor axon exit and aberrant motor axon branching in the zebrafish trunk. Our findings reveal a previously unrecognized role for tnn in spinal motor nerve assembly and expand our understanding of the diverse molecular contributors to spinal motor nerve development and morphogenesis.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Comparative genomics of Sympodiorosea identifies genome evolution mediated through selective pressure on the metabolic gene repertoire. 双角海的比较基因组学鉴定了通过代谢基因库的选择压力介导的基因组进化。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-21 DOI: 10.1093/g3journal/jkag251
Jacoby C Robinson, Aileen Berasategui, Quimi Vidaurre Montoya, Andre Rodrigues, Jeffrey Sosa-Calvo, Zoe Zimmerman, Yuliana Christoper, Hermógenes Fernández-Marín, Timothy D Read, Nicole M Gerardo
{"title":"Comparative genomics of Sympodiorosea identifies genome evolution mediated through selective pressure on the metabolic gene repertoire.","authors":"Jacoby C Robinson, Aileen Berasategui, Quimi Vidaurre Montoya, Andre Rodrigues, Jeffrey Sosa-Calvo, Zoe Zimmerman, Yuliana Christoper, Hermógenes Fernández-Marín, Timothy D Read, Nicole M Gerardo","doi":"10.1093/g3journal/jkag251","DOIUrl":"https://doi.org/10.1093/g3journal/jkag251","url":null,"abstract":"<p><p>Biological interactions involving host-associated fungi are driven by chemistry shaped over evolutionary time. For antagonistic fungi, specialization often involves acquiring genes for novel secretions-including proteins and specialized metabolites-that mediate nutrient acquisition and host defense interactions. Here, we conducted a phylogenomic investigation of Sympodiorosea, ascomycetes commonly found in basal fungus-growing ant gardens. While Sympodiorosea and related genera (Escovopsis, Luteomyces, Manidigitorum, Escovopsioides) are canonically viewed as virulent mycoparasites, non-virulent species may also emerge within these attine-associated fungi. We explored genomic variation in Sympodiorosea to assess potential alternative lifestyles, focusing on the diversity and evolution of metabolic genes. Our study revealed a constrained selective landscape across the Sympodiorosea genome. However, outcomes of in vitro host interactions were diverse and predictable based on the antagonist's ant-species-of-origin, suggesting functional diversification. Phylogenomics indicated that gene gain/loss events in carbohydrate-active enzymes and specialized metabolism drive this diversification. Although selection acts intensely on metabolism-related genes overall, specific metabolic genes experience diversifying selection, indicating their critical role in host associations. Furthermore, Sympodiorosea exhibits protease gene expansions and contractions discordant with a strictly mycoparasitic lifestyle, suggesting either an alternative lifestyle within ant gardens or recent evolution from other niches. These results provide novel insights into fungal genome evolution and the chemistry of the fungus-growing ant symbiosis.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Fruiting under pressure-the 33rd meeting of the Fungal Genetics Conference. 压力下的结果——第33届真菌遗传学会议。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-18 DOI: 10.1093/g3journal/jkag246
Abigail Leavitt LaBella, Jessie MacAlpine, Marie-Claire Harrison, Neha Sahu, Hans Carolus, Leslie Torres Ulloa, Audrey Ward
{"title":"Fruiting under pressure-the 33rd meeting of the Fungal Genetics Conference.","authors":"Abigail Leavitt LaBella, Jessie MacAlpine, Marie-Claire Harrison, Neha Sahu, Hans Carolus, Leslie Torres Ulloa, Audrey Ward","doi":"10.1093/g3journal/jkag246","DOIUrl":"https://doi.org/10.1093/g3journal/jkag246","url":null,"abstract":"","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Age-dependent genetic effects contribute to immunosenescence in Drosophila melanogaster. 年龄依赖性遗传效应促进黑腹果蝇免疫衰老。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-18 DOI: 10.1093/g3journal/jkag258
Shonda Campbell, Isabella Gudino, Mary Rhee, Susan Harbison, Jeff Leips
{"title":"Age-dependent genetic effects contribute to immunosenescence in Drosophila melanogaster.","authors":"Shonda Campbell, Isabella Gudino, Mary Rhee, Susan Harbison, Jeff Leips","doi":"10.1093/g3journal/jkag258","DOIUrl":"https://doi.org/10.1093/g3journal/jkag258","url":null,"abstract":"<p><p>Immunosenescence, the age-related decline in immune function, varies widely among individuals. Although both genetic and environmental factors contribute to variation in immunosenescence, the extent to which age-specific genetic effects shape age-related immune decline remains poorly understood. Here, we tested whether age-related variation in bacterial clearance is shaped by age-dependent genetic effects by measuring clearance of Escherichia coli infection in 175 genotypes at 1 week of age and 183 genotypes at 5 weeks of age. Clearance ability declined with age, but the magnitude of decline differed markedly among genotypes. Age-specific genetic effects explained substantially more phenotypic variation than age-independent genetic differences, and the genetic correlation in clearance ability across ages was modest, indicating that genetic effects on immune performance were only partially shared across ages. Consistent with these findings, genome-wide analyses identified largely distinct sets of candidate genes associated with clearance in young and old flies, including genes exhibiting genotype-by-age effects. Network and gene ontology analyses revealed enrichment for plasma membrane-associated genes and pathways involved in cell adhesion and cell migration. Functional follow-up of 14 candidate genes using hemocyte-specific RNA interference produced limited effects overall but confirmed that nebulosa contributes to bacterial clearance. Together, our results demonstrate that immunosenescence is shaped by age-dependent genetic effects and identify conserved pathways and candidate genes for future mechanistic studies of age-related immune decline.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Stacked enviromic-genomic models improve prediction of genotype performance in new environments. 堆叠环境基因组模型提高了新环境下基因型性能的预测。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-18 DOI: 10.1093/g3journal/jkag257
Marcos Antonio de Godoy Filho, Mauricio Dos Santos Araújo, José Tiago Barroso Chagas, José Baldin Pinheiro
{"title":"Stacked enviromic-genomic models improve prediction of genotype performance in new environments.","authors":"Marcos Antonio de Godoy Filho, Mauricio Dos Santos Araújo, José Tiago Barroso Chagas, José Baldin Pinheiro","doi":"10.1093/g3journal/jkag257","DOIUrl":"https://doi.org/10.1093/g3journal/jkag257","url":null,"abstract":"<p><p>Genotype-by-environment interaction is a major challenge for breeding programs, limiting the predictive ability of genomic selection in untested environments. We propose a Stacked Generalization framework that integrates linear mixed models (factor analytic and genomic best linear unbiased prediction), enviromic reaction norms, and machine learning (Extreme Gradient Boosting) to predict phenotypic plasticity. The framework was evaluated on large multi-environment trials of maize and rice, under scenarios that simulate new environments and seasons. The genetic covariance structures differed between crops, requiring a factor analytic model of order k=6 for continental maize and order k = 2 for the local rice network. Across all scenarios, the Stacking ensemble improved on the genomic baseline (M1), with gains in predictive ability from 10% (r = 0.45$ vs. 0.41 for M1) to 27.5% (r = 0.51 vs. 0.40), and reduced the root mean squared error by 30% to 43% relative to the Enviromic Reaction Norm (M2) when ensembles were selected to minimize error. These gains relied on careful feature engineering. Latent variables from genomic and environmental dimensionality reduction (principal component analysis and PaCMAP) and their interactions were the most important features for the machine learning models, and the first genomic PaCMAP component ranked first for both crops. These results indicate that non-linear dimensionality reduction is a promising tool for genomic and enviromic prediction. By combining the stability of mixed models with the flexibility of machine learning, the framework improves robustness, reduces dependence on any single model, and enhances prediction in new environments, supporting cultivation zone expansion and recommending superior genotypes.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Analysis of proteasome stress in different cell types defines a conserved transcriptional response signature and its modulation with aging. 分析不同细胞类型的蛋白酶体应激定义了一个保守的转录反应特征及其与衰老的调节。
IF 2.4 3区 生物学
G3: Genes|Genomes|Genetics Pub Date : 2026-09-16 DOI: 10.1093/g3journal/jkag245
Mamta Rai, Yong-Dong Wang, Anna Stephan, Anjana Nityanandam, Fabio Demontis
{"title":"Analysis of proteasome stress in different cell types defines a conserved transcriptional response signature and its modulation with aging.","authors":"Mamta Rai, Yong-Dong Wang, Anna Stephan, Anjana Nityanandam, Fabio Demontis","doi":"10.1093/g3journal/jkag245","DOIUrl":"https://doi.org/10.1093/g3journal/jkag245","url":null,"abstract":"<p><p>The proteasome is essential for proteostasis. Transcriptional induction of proteasomal components occurs when the proteasome is inhibited, but an overview of the transcriptional responses caused by proteasome perturbation is missing. Here, we profiled transcriptional changes caused by chemical and genetic proteasome inhibition and defined time-dose responses in cells and organoids. Induction of proteasome components varied by cell type and inhibition mode, whereas other responses were consistent, including upregulation of chaperones and secreted factors, and repression of cell cycle regulators. A proteasome stress response signature was defined based on the genes consistently modulated across systems, and applying this signature to aging datasets revealed activation of this stress response in some tissues, including skeletal muscle. Moreover, secreted factors within the signature showed similar age-related changes in human plasma, suggesting systemic activation of this stress response with aging. Together, these findings define a transcriptional signature for monitoring proteasome stress during aging and age-related diseases.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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