Genes & development最新文献_第5页

Corrigendum: FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity 更正：FIH-1：一种与HIF-1α和VHL相互作用介导HIF-1转录活性抑制的新蛋白

IF 10.5 1区生物学

Genes & development Pub Date : 2025-07-01 DOI: 10.1101/gad.352958.125

Patrick C. Mahon, Kiichi Hirota, Gregg L. Semenza

引用次数: 0

Timing is everything: transcription bursting in development 时间决定一切：转录在发育过程中爆发

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-30 DOI: 10.1101/gad.352465.124

Jee Min Kim, Daniel R. Larson

引用次数: 0

Condensation of human OAS proteins initiates diverse antiviral activities in response to West Nile virus 人类OAS蛋白的缩合启动多种抗病毒活性，以应对西尼罗病毒

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-30 DOI: 10.1101/gad.352725.125

Skyler Briggs, Ebba K. Blomqvist, Andres Cuellar, Derek Correa, James M. Burke

{"title":"Condensation of human OAS proteins initiates diverse antiviral activities in response to West Nile virus","authors":"Skyler Briggs, Ebba K. Blomqvist, Andres Cuellar, Derek Correa, James M. Burke","doi":"10.1101/gad.352725.125","DOIUrl":"https://doi.org/10.1101/gad.352725.125","url":null,"abstract":"Oligoadenylate synthetases (OASs) are ancient proteins that play a critical role in combatting viruses in mammals. OASs are known to antagonize viral replication by binding viral dsRNA and synthesizing 2′–5′-oligo(A), which activates the antiviral endoribonuclease RNase L. Here, we investigate the antiviral activities of the human OAS isoforms (OAS1, OAS2, OAS3, and OASL) during West Nile virus (WNV) infection. We show that OAS3 is the primary OAS isoform required for activating RNase L. OAS3 condensation on dsRNA proximal to WNV replication organelles initiates RNase L activation. OAS3 contains three distinct dsRNA-binding domains that enhance its condensation on dsRNA. The potential for OAS3 to condense on dsRNA is modulated by dsRNA loads and OAS3 expression level, which can be constitutively expressed or induced by type I interferons. OAS1 and OAS2 do not frequently activate RNase L due to their weak potential to condense on dsRNA. However, they assemble into higher-order structures that aggregate full-length ssRNA viral genomes. OASL does not condense on dsRNA. Instead, OASL localizes to processing bodies, stress granules, and RNase L-induced bodies containing host and viral mRNA. These findings define the process of RNase L activation and elucidate the diversity of substrates and functions of human OAS proteins.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"26 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520414","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

Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14 对敲除小鼠的分析揭示了Hippo通路成分PTPN14的关键雌性特异性作用

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-18 DOI: 10.1101/gad.352620.125

Edel M. McCrea, Neoklis Makrides, Takako Tabata, Wencke Reineking, José G. Vilches-Moure, Mengxiong Wang, Julie S. Lake, Hannes Vogel, Brooke Howitt, Xin Zhang, Laura D. Attardi

{"title":"Analysis of knockout mice reveals critical female-specific roles for the Hippo pathway component PTPN14","authors":"Edel M. McCrea, Neoklis Makrides, Takako Tabata, Wencke Reineking, José G. Vilches-Moure, Mengxiong Wang, Julie S. Lake, Hannes Vogel, Brooke Howitt, Xin Zhang, Laura D. Attardi","doi":"10.1101/gad.352620.125","DOIUrl":"https://doi.org/10.1101/gad.352620.125","url":null,"abstract":"The Hippo pathway regulates many physiological processes, including development, tumor suppression, and wound healing. One understudied Hippo pathway component is PTPN14, an evolutionarily conserved tyrosine phosphatase that inhibits YAP/TAZ. Although it is an established tumor suppressor, PTPN14's role in tissue homeostasis has remained unclear. We thus generated Ptpn14-deficient mice and found that only ∼60% of Ptpn14−/− mice survived postnatally, highlighting the importance of PTPN14 for viability while also enabling the discovery of PTPN14 physiological functions. Ptpn14−/− mice developed debilitating corneal lesions and the uterus defect hydrometra, as well as heart and kidney abnormalities. Ptpn14 deficiency precipitated an impaired injury response in the cornea and dysregulated YAP signaling in both the uterus and the cornea. Notably, these phenotypes were female-specific, revealing sexually dimorphic Hippo pathway function through PTPN14. Finally, analysis of human PTPN14 variants suggested that PTPN14's essential roles are conserved in humans, underscoring the importance of our insights for designing therapies to improve women's health.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"15 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319846","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

Sex-specific transcriptome dynamics of Anopheles gambiae during embryonic development 冈比亚按蚊胚胎发育过程中性别特异性转录组动力学

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-18 DOI: 10.1101/gad.352572.124

Agata Izabela Kalita, Eric Marois, Frank Rühle, Claudia Isabelle Keller Valsecchi

{"title":"Sex-specific transcriptome dynamics of Anopheles gambiae during embryonic development","authors":"Agata Izabela Kalita, Eric Marois, Frank Rühle, Claudia Isabelle Keller Valsecchi","doi":"10.1101/gad.352572.124","DOIUrl":"https://doi.org/10.1101/gad.352572.124","url":null,"abstract":"Malaria-transmitting mosquitoes are extremely sexually dimorphic in their anatomy and behavior. Sex-specific gene expression in Anopheles gambiae is well studied in adult stages, but its onset during embryogenesis, apart from sex determination factors like Yob, remains largely unknown. Here, we report a comprehensive single-embryo transcriptome atlas of A. gambiae males and females to understand the earliest stages of establishing the sex-specific expression networks. Our data set reveals embryonic RNA isoform diversity, including a global shift toward distal alternative polyadenylation (APA) event sites during the maternal-to-zygotic genome transition. Sex-biased gene expression and alternative splicing are limited during embryogenesis, with most sex-specific patterns emerging postembryonically. X-chromosome dosage compensation (DC) is established shortly after zygotic genome activation, concomitant with direct binding of the master regulator protein SOA to X-linked promoters. In contrast to known DC regulators in other species, we did not find evidence for early high-affinity sites or distance-dependent patterns in Anopheles. Instead, SOA binding and DC are dynamically specified on genes according to gene activity, where the most strongly expressed genes tend to show the strongest SOA binding. We propose that the Anopheles DC system represents an extreme case of a gene-by-gene regulatory mechanism that operates at the chromosome-wide level.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"147 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319876","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

Opposing lineage specifiers induce a protumor hybrid identity state in lung adenocarcinoma 相反的谱系指示因子诱导肺腺癌的原肿瘤杂交身份状态

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-12 DOI: 10.1101/gad.352742.125

Gabriela Fort, Henry Arnold, Soledad A. Camolotto, Kayla O'Toole, Rushmeen Tariq, Anna Waters, Katherine Gillis, Eric L. Snyder

{"title":"Opposing lineage specifiers induce a protumor hybrid identity state in lung adenocarcinoma","authors":"Gabriela Fort, Henry Arnold, Soledad A. Camolotto, Kayla O'Toole, Rushmeen Tariq, Anna Waters, Katherine Gillis, Eric L. Snyder","doi":"10.1101/gad.352742.125","DOIUrl":"https://doi.org/10.1101/gad.352742.125","url":null,"abstract":"Lineage plasticity is critical for tumor progression and therapy resistance, but the molecular mechanisms underlying cell identity shifts in cancer remain poorly understood. In lung adenocarcinoma (LUAD), the loss of pulmonary lineage fidelity and acquisition of alternate identity programs converge on hybrid identity (hybrid ID) states, which are postulated to be key intermediates in LUAD evolution and are characterized by the coactivation of developmentally incompatible identity programs within individual cells. Here, we uncover a previously unrecognized role for the gastrointestinal transcriptional regulator HNF4α in driving tumor growth and hybrid ID states in LUAD. In LUAD cells expressing the lung lineage specifier NKX2-1, HNF4α induces a GI/liver-like state by directly binding and activating its canonical targets. HNF4α also disrupts NKX2-1 genomic localization and dampens pulmonary identity within hybrid ID LUAD. We show that this hybrid ID state is maintained by sustained RAS/MEK signaling. Inhibition of the RAS/MEK signaling cascade augments NKX2-1 chromatin binding at pulmonary-specific genes and induces drug resistance-associated pulmonary signatures. Finally, we demonstrate that HNF4α depletion sensitizes LUAD cells to KRASG12D inhibition. Collectively, our data show that coexpression of opposing lineage specifiers is a novel mechanism of identity dysregulation in LUAD that influences both tumor progression and response to targeted therapy.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"39 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278221","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

ELAV mediates circular RNA biogenesis in neurons ELAV介导神经元中环状RNA的生物发生

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-09 DOI: 10.1101/gad.352670.125

Carlos Alfonso-Gonzalez, Mengjin Shi, Sakshi Gorey, Sarah Holec, Judit Carrasco, Michael Rauer, Stylianos Tsagkris, Fernando Mateos, Valérie Hilgers

引用次数: 0

Corrigendum: The glucose-sensing transcription factor MLX promotes myogenesis via myokine signaling 更正：葡萄糖感应转录因子MLX通过肌因子信号传导促进肌肉发生

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-01 DOI: 10.1101/gad.352856.125

Liam C. Hunt, Beisi Xu, David Finkelstein, Yiping Fan, Patrick A. Carroll, Pei-Feng Cheng, Robert N. Eisenman, Fabio Demontis

引用次数: 0

Retraction: Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes 回顾：UVB照射后的翻译重编程是由DNA- pkcs介导的，并允许选择性招募编码DNA修复酶的mrna的多体

IF 10.5 1区生物学

Genes & development Pub Date : 2025-06-01 DOI: 10.1101/gad.352836.125

Ian R. Powley, Alexander Kondrashov, Lucy A. Young, Helen C. Dobbyn, Kirsti Hill, Ian G. Cannell, Mark Stoneley, Yi-Wen Kong, Julia A. Cotes, Graeme C.M. Smith, Ron Wek, Christopher Hayes, Timothy W. Gant, Keith A. Spriggs, Martin Bushell, Anne E. Willis

引用次数: 0

NOTCH1 S2513 is critical for the regulation of NICD levels impacting the segmentation clock in hiPSC-derived PSM cells and somitoids NOTCH1 S2513对NICD水平的调控至关重要，影响hipsc衍生的PSM细胞和体质体的分割时钟

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-29 DOI: 10.1101/gad.352909.125

Hedda A. Meijer, Adam Hetherington, Sara J. Johnson, Rosie L. Gallagher, Izzah N. Hussein, Yuqi Weng, Jess M. Rae, Tomas E.J.C. Noordzij, Margarita Kalamara, Thomas J. Macartney, Lindsay Davidson, David M.A. Martin, Marek Gierlinski, Paul Davies, Katharina F. Sonnen, Philip J. Murray, J. Kim Dale

{"title":"NOTCH1 S2513 is critical for the regulation of NICD levels impacting the segmentation clock in hiPSC-derived PSM cells and somitoids","authors":"Hedda A. Meijer, Adam Hetherington, Sara J. Johnson, Rosie L. Gallagher, Izzah N. Hussein, Yuqi Weng, Jess M. Rae, Tomas E.J.C. Noordzij, Margarita Kalamara, Thomas J. Macartney, Lindsay Davidson, David M.A. Martin, Marek Gierlinski, Paul Davies, Katharina F. Sonnen, Philip J. Murray, J. Kim Dale","doi":"10.1101/gad.352909.125","DOIUrl":"https://doi.org/10.1101/gad.352909.125","url":null,"abstract":"The segmentation clock is a molecular oscillator that regulates the timing of somite formation in the developing vertebrate embryo. NOTCH signaling is one of the key pathways required for proper functioning of the segmentation clock. Aberrant NOTCH signaling results in developmental abnormalities such as congenital scoliosis as well as diseases such as T-cell acute lymphoblastic lymphoma (T-ALL). In this study, we analyzed the effects of a mutation detected in T-ALL patients on somitogenesis using human iPSC-derived PSM cells and somitoids. Mutation of NOTCH1 serine 2513 into alanine compromises the interaction of Notch intracellular domain (NICD) with the F-box protein FBXW7 and consequently increases NICD stability and NICD levels in PSM cells. Moreover, the mutation impairs several aspects of clock gene oscillations such as signal intensity, periodicity, directionality of the oscillations, and the ability to sustain oscillations. Furthermore, it restricts the ability of somitoids to polarize, elongate, and form paired segments. The data suggest a mechanism by which post-translational modification of a key segmentation clock component plays a crucial role in vertebrate axis segmentation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"57 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176601","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