EMBO Reports最新文献_第4页

Induction of a transcriptional adaptation response by RNA destabilization events. RNA不稳定事件诱导的转录适应反应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1038/s44319-025-00427-3

Lihan Xie, Gabrielius Jakutis, Christopher M Dooley, Stefan Guenther, Zacharias Kontarakis, Sarah P Howard, Thomas Juan, Didier Y R Stainier

{"title":"Induction of a transcriptional adaptation response by RNA destabilization events.","authors":"Lihan Xie, Gabrielius Jakutis, Christopher M Dooley, Stefan Guenther, Zacharias Kontarakis, Sarah P Howard, Thomas Juan, Didier Y R Stainier","doi":"10.1038/s44319-025-00427-3","DOIUrl":"10.1038/s44319-025-00427-3","url":null,"abstract":"Transcriptional adaptation (TA) is a cellular process whereby mRNA-destabilizing mutations are associated with the transcriptional upregulation of so-called adapting genes. The nature of the TA-triggering factor(s) remains unclear, namely whether an mRNA-borne premature termination codon or the subsequent mRNA decay process, and/or its products, elicits TA. Here, working with mouse Actg1, we first establish two types of perturbations that lead to mRNA destabilization: Cas9-induced mutations predicted to lead to mutant mRNA decay, and Cas13d-mediated mRNA cleavage. We find that both types of perturbations are effective in degrading Actg1 mRNA, and that they both upregulate Actg2. Notably, increased chromatin accessibility at the Actg2 locus was observed only in the Cas9-induced mutant cells but not in the Cas13d-targeted cells, suggesting that chromatin remodeling is not required for Actg2 upregulation. We further show that ribozyme-mediated Actg1 pre-mRNA cleavage also leads to a robust upregulation of Actg2, and that this upregulation is again independent of chromatin remodeling. Together, these data highlight the critical role of RNA destabilization events as a trigger for TA, or at least a TA-like response.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2262-2279"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699922","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

Dynamic interaction of MYC enhancer RNA with YEATS2 protein regulates MYC gene transcription in pancreatic cancer. MYC增强子RNA与YEATS2蛋白的动态相互作用调控胰腺癌中MYC基因的转录

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-11 DOI: 10.1038/s44319-025-00446-0

Jayita Roy, Aniket Kumar, Shouvik Chakravarty, Nidhan K Biswas, Srikanta Goswami, Anup Mazumder

{"title":"Dynamic interaction of MYC enhancer RNA with YEATS2 protein regulates MYC gene transcription in pancreatic cancer.","authors":"Jayita Roy, Aniket Kumar, Shouvik Chakravarty, Nidhan K Biswas, Srikanta Goswami, Anup Mazumder","doi":"10.1038/s44319-025-00446-0","DOIUrl":"10.1038/s44319-025-00446-0","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is one of the most prevalent and aggressive forms of pancreatic cancer with low survival rates and limited treatment options. Aberrant expression of the MYC oncogene promotes PDAC progression. Recent reports have established a role for enhancer RNAs (eRNAs), originating from active enhancers, in controlling gene transcription. Here we show that a novel MYC eRNA regulates MYC gene expression during chronic inflammatory conditions in pancreatic cancer cells. A higher amount of MYC eRNA is observed in chronic pancreatitis and in pancreatic cancer patients. We show that MYC eRNA interacts with YEATS2, a histone reader protein of the ATAC-HAT complex, and augments the association of YEATS2-containing ATAC complexes with MYC promoter/enhancer regions and thus increases MYC gene expression. TNF-α induced Tyrosine dephosphorylation of the YEATS domain increases MYC eRNA binding to the YEATS2 protein in pancreatic cancer cells. Our study adds another regulatory layer of MYC gene expression by enhancer-driven transcription.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2519-2544"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971900","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

Genotoxic stress triggers Scd6-dependent regulation of translation to modulate the DNA damage response. 基因毒性应激触发依赖于scd6的翻译调控来调节DNA损伤反应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-24 DOI: 10.1038/s44319-025-00443-3

Gayatri Mohanan, Raju Roy, Hélène Malka-Mahieu, Swati Lamba, Lucilla Fabbri, Sidhant Kalia, Anusmita Biswas, Sylvain Martineau, Céline M Labbé, Stéphan Vagner, Purusharth I Rajyaguru

{"title":"Genotoxic stress triggers Scd6-dependent regulation of translation to modulate the DNA damage response.","authors":"Gayatri Mohanan, Raju Roy, Hélène Malka-Mahieu, Swati Lamba, Lucilla Fabbri, Sidhant Kalia, Anusmita Biswas, Sylvain Martineau, Céline M Labbé, Stéphan Vagner, Purusharth I Rajyaguru","doi":"10.1038/s44319-025-00443-3","DOIUrl":"10.1038/s44319-025-00443-3","url":null,"abstract":"The role of mRNA translation and decay in the genotoxic stress response remains poorly explored. Here, we identify the role of yeast RGG motif-containing RNA binding protein Scd6 and its human ortholog LSM14A in genotoxic stress response. Scd6 localizes to cytoplasmic puncta upon cell treatment with various genotoxic agents. Scd6 genetically interacts with SRS2, a DNA helicase with an anti-recombination role in DNA damage repair under HU stress. Scd6 directly interacts with the SRS2 mRNA to repress its translation in cytoplasmic granules upon HU stress in an eIF4G1-independent manner. Scd6-SRS2 interaction is modulated by arginine methylation and the LSm-domain of Scd6, which acts as a cis-regulator of Scd6 arginine methylation. LSM14A regulates the translation of mRNAs encoding key NHEJ (Non-homologous end-joining) proteins such as RTEL1 (SRS2 functional homolog) and LIG4. NHEJ activity in yeast and mammalian cells is regulated by Scd6 and LSM14A, respectively. Overall, this report unveils the role of RNA binding proteins in regulating the translation of specific mRNAs coding for DNA damage response proteins upon genotoxic stress.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2715-2739"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990546","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

Distinct pathogenic mutations in ARF1 allow dissection of its dual role in cGAS-STING signalling. ARF1中不同的致病突变允许解剖其在cGAS-STING信号传导中的双重作用。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1038/s44319-025-00423-7

Johannes Lang, Tim Bergner, Julia Zinngrebe, Alice Lepelley, Katharina Vill, Steffen Leiz, Meinhard Wlaschek, Matias Wagner, Karin Scharffetter-Kochanek, Pamela Fischer-Posovszky, Clarissa Read, Yanick J Crow, Maximilian Hirschenberger, Konstantin M J Sparrer

{"title":"Distinct pathogenic mutations in ARF1 allow dissection of its dual role in cGAS-STING signalling.","authors":"Johannes Lang, Tim Bergner, Julia Zinngrebe, Alice Lepelley, Katharina Vill, Steffen Leiz, Meinhard Wlaschek, Matias Wagner, Karin Scharffetter-Kochanek, Pamela Fischer-Posovszky, Clarissa Read, Yanick J Crow, Maximilian Hirschenberger, Konstantin M J Sparrer","doi":"10.1038/s44319-025-00423-7","DOIUrl":"10.1038/s44319-025-00423-7","url":null,"abstract":"Tight control of cGAS-STING-mediated DNA sensing is crucial to avoid auto-inflammation. The GTPase ADP-ribosylation factor 1 (ARF1) is crucial to maintain cGAS-STING homeostasis and various pathogenic ARF1 variants are associated with type I interferonopathies. Functional ARF1 inhibits STING activity by maintaining mitochondrial integrity and facilitating COPI-mediated retrograde STING trafficking and deactivation. Yet the factors governing the two distinct functions of ARF1 remained unexplored. Here, we dissect ARF1's dual role by a comparative analysis of disease-associated ARF1 variants and their impact on STING signalling. We identify a de novo heterozygous s.55 C > T/p.R19C ARF1 variant in a patient with type I interferonopathy symptoms. The GTPase-deficient variant ARF1 R19C selectively disrupts COPI binding and retrograde transport of STING, thereby prolonging innate immune activation without affecting mitochondrial integrity. Treatment of patient fibroblasts in vitro with the STING signalling inhibitors H-151 and amlexanox reduces chronic interferon signalling. Summarizing, our data reveal the molecular basis of a ARF1-associated type I interferonopathy allowing dissection of the two roles of ARF1, and suggest that pharmacological targeting of STING may alleviate ARF1-associated auto-inflammation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2232-2261"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699919","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

Molecular basis for assembly and activation of the Hook3 - KIF1C complex-dependent transport machinery. Hook3 - KIF1C复合物依赖性转运机制的组装和激活的分子基础。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 DOI: 10.1038/s44319-025-00458-w

Hye Seon Lee, Daseuli Yu, Kyoung Eun Baek, Ho-Chul Shin, Seung Jun Kim, Won Do Heo, Bonsu Ku

{"title":"Molecular basis for assembly and activation of the Hook3 - KIF1C complex-dependent transport machinery.","authors":"Hye Seon Lee, Daseuli Yu, Kyoung Eun Baek, Ho-Chul Shin, Seung Jun Kim, Won Do Heo, Bonsu Ku","doi":"10.1038/s44319-025-00458-w","DOIUrl":"https://doi.org/10.1038/s44319-025-00458-w","url":null,"abstract":"Microtubule-associated cargo transport, a central process governing the localization and movement of various cellular cargoes, is orchestrated by the coordination of two types of motor proteins (kinesins and dyneins), along with diverse adaptor and accessory proteins. Hook microtubule tethering protein 3 (Hook3) is a cargo adaptor that serves as a scaffold for recruiting kinesin family member 1C (KIF1C) and dynein, thereby regulating bidirectional cargo transport. Herein, we conduct structural and functional analyses of how Hook3 mediates KIF1C-dependent anterograde cargo transport through interaction with KIF1C and PTPN21. We verify the interactions among the three proteins and determine the crystal structure of the Hook3(553-624) - KIF1C(714-809) complex. Subsequent structure-based mutational analysis demonstrates that this complex formation is necessary and sufficient for the interaction between the full-length proteins in HEK293T cells and plays a key role in Hook3- and KIF1C-mediated anterograde transport in RPE1 cells. Thus, this study provides a basis for a comprehensive understanding of how Hook3 cooperates with other components during the initial steps of activation and assembly of the Hook3- and KIF1C-dependent cargo transport machinery.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990550","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

HDAC6 deacetylates ENKD1 to regulate mitotic spindle behavior and corneal epithelial homeostasis. HDAC6使ENKD1去乙酰化，调节有丝分裂纺锤体行为和角膜上皮稳态。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1038/s44319-025-00438-0

Ting Song, Xueqing Han, Hanxiao Yin, Junkui Zhao, Mingming Ma, Xiaonuan Wen, Chunli Liu, Yiyang Yue, Huijie Zhao, Jun Zhou, Yang Yang, Jie Ran, Min Liu

{"title":"HDAC6 deacetylates ENKD1 to regulate mitotic spindle behavior and corneal epithelial homeostasis.","authors":"Ting Song, Xueqing Han, Hanxiao Yin, Junkui Zhao, Mingming Ma, Xiaonuan Wen, Chunli Liu, Yiyang Yue, Huijie Zhao, Jun Zhou, Yang Yang, Jie Ran, Min Liu","doi":"10.1038/s44319-025-00438-0","DOIUrl":"10.1038/s44319-025-00438-0","url":null,"abstract":"Corneal diseases can cause severe visual impairment and even blindness, which have been linked to the interruption of corneal epithelial homeostasis. However, the underlying molecular mechanisms are largely unknown. In this study, by comparing the transcriptomes of keratoconus, bacterial keratitis, viral keratitis, and healthy corneas, we found a steady upregulation of histone deacetylase 6 (HDAC6) in corneal diseases. Consistently, a significant increase in HDAC6 was observed in mouse corneas with bacterial keratitis. Overexpression of HDAC6 in mice results in a significant thickening of the corneal epithelium. Mechanistic studies reveal that HDAC6 overexpression disrupts mitotic spindle orientation and positioning in corneal epithelial cells. Our data further show that HDAC6 deacetylates enkurin domain-containing protein 1 (ENKD1) at lysine 98 and thereby impedes its interaction with γ-tubulin, restraining the centrosomal localization of ENKD1 and its proper function in regulating mitotic spindle behavior. These findings uncover a pivotal role for HDAC6-mediated deacetylation of ENKD1 in the control of corneal epithelial homeostasis, providing potential therapeutic targets for treating corneal diseases.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2597-2621"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742654","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

Root stem cell homeostasis in Arabidopsis involves cell-type specific transcription factor complexes. 拟南芥根干细胞稳态涉及细胞类型特异性转录因子复合物。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-19 DOI: 10.1038/s44319-025-00422-8

Vivien I Strotmann, Monica L García-Gómez, Yvonne Stahl

{"title":"Root stem cell homeostasis in Arabidopsis involves cell-type specific transcription factor complexes.","authors":"Vivien I Strotmann, Monica L García-Gómez, Yvonne Stahl","doi":"10.1038/s44319-025-00422-8","DOIUrl":"10.1038/s44319-025-00422-8","url":null,"abstract":"In Arabidopsis thaliana the root stem cell niche (SCN) is maintained by a complex regulatory network crucial for growth and developmental plasticity. However, many aspects of this network, particularly concerning stem cell quiescence and replenishment, remain unclear. Here, we investigate the interactions of key transcription factors (TFs) BRASSINOSTEROID AT VASCULAR AND ORGANIZING CENTRE (BRAVO), PLETHORA 3 (PLT3), and WUSCHEL-RELATED HOMEOBOX 5 (WOX5) in SCN maintenance. Analysis of mutants reveals their combinatorial regulation of cell fates and divisions in the SCN. In addition, studies using Fluorescence Resonance Energy Transfer Fluorescence Lifetime Imaging Microscopy (FRET-FLIM) in combination with novel analysis methods enable us to quantify protein-protein interaction (PPI) affinities and higher-order complex formation among these TFs. Our findings were integrated into a computational model, indicating that cell-type specific protein complex profiles and formations, influenced by prion-like domains in PLT3, play an important role in regulating the SCN. We propose that these unique protein complex signatures may serve as indicators of cell specificity, enriching the regulatory network that governs stem cell maintenance and replenishment in the Arabidopsis root.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2323-2346"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663008","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

Lack of AtMC1 catalytic activity triggers autoimmunity dependent on NLR stability. 缺乏 AtMC1 催化活性会引发依赖于 NLR 稳定性的自身免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1038/s44319-025-00426-4

Jose Salguero-Linares, Laia Armengot, Joel Ayet, Nerea Ruiz-Solaní, Svenja C Saile, Marta Salas-Gómez, Esperanza Fernandez, Lode Denolf, Fernando Navarrete, Jenna Krumbach, Markus Kaiser, Simon Stael, Frank Van Breusegem, Kris Gevaert, Farnusch Kaschani, Morten Petersen, Farid El Kasmi, Marc Valls, Núria S Coll

{"title":"Lack of AtMC1 catalytic activity triggers autoimmunity dependent on NLR stability.","authors":"Jose Salguero-Linares, Laia Armengot, Joel Ayet, Nerea Ruiz-Solaní, Svenja C Saile, Marta Salas-Gómez, Esperanza Fernandez, Lode Denolf, Fernando Navarrete, Jenna Krumbach, Markus Kaiser, Simon Stael, Frank Van Breusegem, Kris Gevaert, Farnusch Kaschani, Morten Petersen, Farid El Kasmi, Marc Valls, Núria S Coll","doi":"10.1038/s44319-025-00426-4","DOIUrl":"10.1038/s44319-025-00426-4","url":null,"abstract":"Plants utilize cell surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors to detect non-self and elicit robust immune responses. Fine-tuning the homeostasis of these receptors is critical to prevent their hyperactivation. Here, we show that Arabidopsis plants lacking metacaspase 1 (AtMC1) display autoimmunity dependent on immune signalling components downstream of NLR and PRR activation. Overexpression of a catalytically inactive AtMC1 in an atmc1 background triggers severe autoimmunity partially dependent on the same immune signalling components. Overexpression of the E3 ligase SNIPER1, a master regulator of NLR homeostasis, fully reverts the AtMC1-dependent autoimmunity phenotype, inferring that a broad defect in NLR turnover may underlie the severe phenotype observed. Catalytically inactive AtMC1 localizes to punctate structures that are degraded through autophagy. Considering also previous evidence on the proteostatic functions of AtMC1, we speculate that Wt AtMC1 may either directly or indirectly control NLR protein levels, thereby preventing autoimmunity.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2378-2412"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669185","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

Reciprocal rescue of Wolfram syndrome by two causative genes. 两个致病基因对Wolfram综合征的相互挽救。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-03 DOI: 10.1038/s44319-025-00436-2

Su Jin Ham, Eunju Yoon, Da Hyun Lee, Sehyeon Kim, Heesuk Yoo, Jongkyeong Chung

{"title":"Reciprocal rescue of Wolfram syndrome by two causative genes.","authors":"Su Jin Ham, Eunju Yoon, Da Hyun Lee, Sehyeon Kim, Heesuk Yoo, Jongkyeong Chung","doi":"10.1038/s44319-025-00436-2","DOIUrl":"10.1038/s44319-025-00436-2","url":null,"abstract":"Wolfram syndrome (WS) is marked by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. The causative genes, WFS1 and CISD2, correspond to WS types 1 and 2, respectively. Here, we establish their mutual indispensability for inositol 1,4,5-triphosphate receptor (IP3R) activity, demonstrating their ability to restore reduced IP3R activity in WFS1- or CISD2-deficient mammalian cells. Additionally, our Drosophila WS models lacking dWFS1 or dCISD exhibit diabetes-like phenotypes analogous to WS patients, and overexpression of dWFS1 and dCISD in the flies alleviates their phenotypes. We have engineered a peptide containing the CDGSH domain of CISD2, critical for its interaction with IP3R. Overexpression of our CISD2 peptide or treatment with its cell-penetrating peptide (CPP)-conjugated form restores calcium homeostasis in WFS1- or CISD2-deficient cells, and overexpressing the homologous dCISD peptide suppresses diabetes-like phenotypes in WS model flies. These findings underscore the intricate involvements of WFS1 and CISD2 in ER calcium regulation and provide potential therapeutic prospects for WS-related diabetes.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"2459-2482"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779533","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

S100PBP interacts with nucleoporin TPR and facilitates XY crossover formation in mice. S100PBP与核孔蛋白TPR相互作用，促进小鼠XY交叉形成。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-01 Epub Date: 2025-04-09 DOI: 10.1038/s44319-025-00391-y

Yufan Wu, Yang Li, Huan Zhang, Jingwei Ye, Ming Li, Jianteng Zhou, Xuefeng Xie, Hao Yin, Min Chen, Gang Yang, Suixing Fan, Baolu Shi, Hanwei Jiang, Qinghua Shi, Hui Ma

{"title":"S100PBP interacts with nucleoporin TPR and facilitates XY crossover formation in mice.","authors":"Yufan Wu, Yang Li, Huan Zhang, Jingwei Ye, Ming Li, Jianteng Zhou, Xuefeng Xie, Hao Yin, Min Chen, Gang Yang, Suixing Fan, Baolu Shi, Hanwei Jiang, Qinghua Shi, Hui Ma","doi":"10.1038/s44319-025-00391-y","DOIUrl":"10.1038/s44319-025-00391-y","url":null,"abstract":"During meiosis, at least one crossover is selectively generated per pair of homologous chromosomes through homologous recombination to ensure their faithful segregation. The molecular mechanisms controlling meiotic recombination, particularly in XY chromosomes that share a tiny region of homology (i.e., the pseudoautosomal region, PAR), remain poorly understood. Here, we identify S100PBP as a key modulator of both XY and autosomal recombination in mice. S100pbp-knockout mice exhibit male infertility and spermatogenesis arrest at meiotic metaphase I, resulting from a drastic reduction in XY crossovers. This failure in XY crossover formation is due to a reduction in TEX11/M1AP-bound recombination intermediates at the PAR. By contrast, disruption of S100PBP significantly increases the number of recombination intermediates and crossovers on autosomes. Co-immunoprecipitation mass spectrometry revealed that S100PBP interacts with the nucleoporin TPR. Furthermore, S100PBP is localized specifically to the nuclear pores of meiocytes, likely in a TPR-dependent manner. These findings demonstrate that S100PBP promotes XY crossover formation while limiting excess autosomal crossovers and shed light on the potential role of nuclear pores in regulating meiotic recombination.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":"26 9","pages":"2280-2299"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964487","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