Pub Date : 2025-12-18DOI: 10.1016/j.jbc.2025.110957
Alvaro Garcia, Bogdan Lev, Khondker R Hossain, Amy Gorman, Dil Diaz, Thi Hanh Nguyen Pham, Flemming Cornelius, Toby W Allen, Ronald J Clarke
{"title":"Correction: Cholesterol depletion inhibits Na+,K+-ATPase activity in a near-native membrane environment.","authors":"Alvaro Garcia, Bogdan Lev, Khondker R Hossain, Amy Gorman, Dil Diaz, Thi Hanh Nguyen Pham, Flemming Cornelius, Toby W Allen, Ronald J Clarke","doi":"10.1016/j.jbc.2025.110957","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110957","url":null,"abstract":"","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"302 1","pages":"110957"},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.jbc.2025.111064
Sendi Rafael Adame-Garcia,Thomas S Hoang,Pham Thuy Thien Vo,Valeria Burghi,Rodolfo Daniel Cervantes-Villagrana,Lennis Beatriz Orduña-Castillo,Dana J Ramms,JoAnn Trejo,J Silvio Gutkind
Cyclooxygenase-2 (COX-2/PTGS2) is an inducible enzyme central to inflammatory responses, and its expression is tightly regulated. Elevated intracellular cAMP levels are known to stimulate COX-2 expression. However, the precise mechanism by which protein kinase A (PKA), the primary cAMP effector, mediates this process remains elusive. In this study, we investigated the role of PKA in regulating COX-2 expression in macrophages. We found that PKA activity is essential for COX-2 expression, primarily through a post-transcriptional mechanism that enhances COX-2 mRNA stability. This effect is mediated by the interaction between PKA and the RNA-binding proteins HuR (ELAVL1) and TTP (tristetraprolin/ZFP36). Specifically, we observed that the catalytic subunit of PKA directly interacts with HuR, a well-established COX-2 mRNA stabilizer. PKA activation increased HuR binding to COX-2 mRNA, and pharmacological inhibition of HuR abrogated COX-2 expression in macrophages stimulated with PGE2 and IL-1β. Furthermore, PKA stimulates the phosphorylation of TTP, an mRNA-destabilizing protein, thereby reducing its binding to the COX-2 transcript. We propose that PKA enhances COX-2 expression by interacting with HuR, maintaining proximity to COX-2 mRNA, and protecting it from TTP-mediated destabilization. Our findings reveal a mechanistic link between PKA activity and COX-2 mRNA stability through HuR and TTP, highlighting the role of RNA-binding proteins as novel effectors of PKA signaling in post-transcriptional regulation.
{"title":"Protein Kinase A regulates Cyclooxygenase-2 expression through the RNA-binding proteins HuR and TTP.","authors":"Sendi Rafael Adame-Garcia,Thomas S Hoang,Pham Thuy Thien Vo,Valeria Burghi,Rodolfo Daniel Cervantes-Villagrana,Lennis Beatriz Orduña-Castillo,Dana J Ramms,JoAnn Trejo,J Silvio Gutkind","doi":"10.1016/j.jbc.2025.111064","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.111064","url":null,"abstract":"Cyclooxygenase-2 (COX-2/PTGS2) is an inducible enzyme central to inflammatory responses, and its expression is tightly regulated. Elevated intracellular cAMP levels are known to stimulate COX-2 expression. However, the precise mechanism by which protein kinase A (PKA), the primary cAMP effector, mediates this process remains elusive. In this study, we investigated the role of PKA in regulating COX-2 expression in macrophages. We found that PKA activity is essential for COX-2 expression, primarily through a post-transcriptional mechanism that enhances COX-2 mRNA stability. This effect is mediated by the interaction between PKA and the RNA-binding proteins HuR (ELAVL1) and TTP (tristetraprolin/ZFP36). Specifically, we observed that the catalytic subunit of PKA directly interacts with HuR, a well-established COX-2 mRNA stabilizer. PKA activation increased HuR binding to COX-2 mRNA, and pharmacological inhibition of HuR abrogated COX-2 expression in macrophages stimulated with PGE2 and IL-1β. Furthermore, PKA stimulates the phosphorylation of TTP, an mRNA-destabilizing protein, thereby reducing its binding to the COX-2 transcript. We propose that PKA enhances COX-2 expression by interacting with HuR, maintaining proximity to COX-2 mRNA, and protecting it from TTP-mediated destabilization. Our findings reveal a mechanistic link between PKA activity and COX-2 mRNA stability through HuR and TTP, highlighting the role of RNA-binding proteins as novel effectors of PKA signaling in post-transcriptional regulation.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"48 1","pages":"111064"},"PeriodicalIF":4.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.jbc.2025.110955
Roxane Jacobs, Gaëtan Herinckx, Noémie Galland, Clémence Balty, Didier Vertommen, Mark H Rider, Manuel Johanns
{"title":"Correction: Combined deletion of cytosolic 5'-nucleotidases IA and II lowers glycemia by improving skeletal muscle insulin action and lowering hepatic glucose production.","authors":"Roxane Jacobs, Gaëtan Herinckx, Noémie Galland, Clémence Balty, Didier Vertommen, Mark H Rider, Manuel Johanns","doi":"10.1016/j.jbc.2025.110955","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110955","url":null,"abstract":"","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"302 1","pages":"110955"},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Post-translational modifications (PTMs) of the glycolytic enzyme phosphofructokinase, liver type (PFKL) play a vital role in regulating its activity and function. Recently, we observed a reduction of PFKL acetylation in platelet-derived growth factor (PDGF)-BB-induced synthetic vascular smooth muscle cells (VSMCs). However, the function of acetylated PFKL has not be defined. This study aims to elucidate the effects and mechanisms of PFKL acetylation on development and progression of vascular diseases. We found that the expression of PFKL is up-regulated and its acetylation level is decreased in PDGF-BB-induced proliferative VSMCs. HDAC6, acts as the deacetylase of PFKL, could interact with PFKL to enhance enzymatic activity of PFKL by accelerating PFKL tetrameric formation and aerobic glycolysis process, thereby promoting VSMC proliferation, which can be hindered through the application of HDAC inhibitor Trichostatin A (TSA) or siHDAC6. Site prediction and experimental validation revealed that K563 was the main PFKL acetylation site. The recombinant adenoviral vector carrying PFKL K563R mutant aggravated, while the K563Q mutant attenuated PDGF-BB-induced VSMC proliferation and ligation-induced neointimal formation. Thus, PFKL may be a potential target for vascular reconstruction diseases treatment.
肝型糖酵解酶磷酸果糖激酶（PFKL）的翻译后修饰（PTMs）在调节其活性和功能中起着至关重要的作用。最近，我们观察到血小板衍生生长因子(PDGF)- bb诱导的合成血管平滑肌细胞（VSMCs）中PFKL乙酰化降低。然而，乙酰化PFKL的功能尚未明确。本研究旨在阐明PFKL乙酰化在血管疾病发生发展中的作用及其机制。我们发现pdgf - bb诱导的增殖性VSMCs中PFKL的表达上调，其乙酰化水平降低。HDAC6作为PFKL的去乙酰化酶，可与PFKL相互作用，通过加速PFKL四聚体的形成和有氧糖酵解过程，增强PFKL的酶活性，从而促进VSMC的增殖，可通过HDAC抑制剂Trichostatin A （TSA）或siHDAC6的应用加以抑制。位点预测和实验验证表明，K563是PFKL乙酰化的主要位点。携带PFKL的重组腺病毒载体K563R突变体增强，而K563Q突变体减弱pdgf - bb诱导的VSMC增殖和结扎诱导的内膜形成。因此，PFKL可能是血管重建疾病治疗的潜在靶点。
{"title":"HDAC6-mediated PFKL deacetylation enhances aerobic glycolysis and promotes VSMC proliferation.","authors":"Zhao-Kun Hu,Zhi-Yan Ren,Jie-Xin Pang,Hui Li,Meng-Nan Yang,Li-Hua Dong","doi":"10.1016/j.jbc.2025.111075","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.111075","url":null,"abstract":"Post-translational modifications (PTMs) of the glycolytic enzyme phosphofructokinase, liver type (PFKL) play a vital role in regulating its activity and function. Recently, we observed a reduction of PFKL acetylation in platelet-derived growth factor (PDGF)-BB-induced synthetic vascular smooth muscle cells (VSMCs). However, the function of acetylated PFKL has not be defined. This study aims to elucidate the effects and mechanisms of PFKL acetylation on development and progression of vascular diseases. We found that the expression of PFKL is up-regulated and its acetylation level is decreased in PDGF-BB-induced proliferative VSMCs. HDAC6, acts as the deacetylase of PFKL, could interact with PFKL to enhance enzymatic activity of PFKL by accelerating PFKL tetrameric formation and aerobic glycolysis process, thereby promoting VSMC proliferation, which can be hindered through the application of HDAC inhibitor Trichostatin A (TSA) or siHDAC6. Site prediction and experimental validation revealed that K563 was the main PFKL acetylation site. The recombinant adenoviral vector carrying PFKL K563R mutant aggravated, while the K563Q mutant attenuated PDGF-BB-induced VSMC proliferation and ligation-induced neointimal formation. Thus, PFKL may be a potential target for vascular reconstruction diseases treatment.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"7 1","pages":"111075"},"PeriodicalIF":4.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.jbc.2025.110973
Henry Sawczyc, Spyridon Kosteletos, Adam Lange
{"title":"Correction: Death, taxes, and rhomboids: Understanding the ubiquitous roles of the rhomboid protein superfamily.","authors":"Henry Sawczyc, Spyridon Kosteletos, Adam Lange","doi":"10.1016/j.jbc.2025.110973","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110973","url":null,"abstract":"","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"302 1","pages":"110973"},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.jbc.2025.111067
Jacob W Smith,Damien B Wilburn,Vladislav Belyy
Inositol-requiring enzyme 1 (IRE1) is one of three known sensor proteins that respond to homeostatic perturbations in the metazoan endoplasmic reticulum. The three sensors collectively initiate an intertwined signaling network called the Unfolded Protein Response (UPR). Although IRE1 plays pivotal roles in human health and development, understanding its specific contributions to the UPR remains a challenge due to signaling crosstalk from the other two stress sensors. To overcome this problem, we engineered a light-activatable version of IRE1 and probed the transcriptomic effects of IRE1 activity in isolation from the other branches of the UPR. We demonstrate that 1) oligomerization alone is sufficient to activate IRE1 in human cells, 2) IRE1's transcriptional response evolves substantially under prolonged activation, and 3) the UPR induces major changes in mRNA splice isoform abundance in an IRE1-independent manner. Our data reveal previously unknown targets of IRE1's transcriptional regulation and direct degradation. Additionally, the tools developed here will be broadly applicable for precise dissection of the UPR in diverse cell types, tissues, and organisms.
{"title":"Direct Optical Activation of Human IRE1 Identifies Unique Patterns of Transcriptional and Post-Transcriptional mRNA Regulation in the Unfolded Protein Response.","authors":"Jacob W Smith,Damien B Wilburn,Vladislav Belyy","doi":"10.1016/j.jbc.2025.111067","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.111067","url":null,"abstract":"Inositol-requiring enzyme 1 (IRE1) is one of three known sensor proteins that respond to homeostatic perturbations in the metazoan endoplasmic reticulum. The three sensors collectively initiate an intertwined signaling network called the Unfolded Protein Response (UPR). Although IRE1 plays pivotal roles in human health and development, understanding its specific contributions to the UPR remains a challenge due to signaling crosstalk from the other two stress sensors. To overcome this problem, we engineered a light-activatable version of IRE1 and probed the transcriptomic effects of IRE1 activity in isolation from the other branches of the UPR. We demonstrate that 1) oligomerization alone is sufficient to activate IRE1 in human cells, 2) IRE1's transcriptional response evolves substantially under prolonged activation, and 3) the UPR induces major changes in mRNA splice isoform abundance in an IRE1-independent manner. Our data reveal previously unknown targets of IRE1's transcriptional regulation and direct degradation. Additionally, the tools developed here will be broadly applicable for precise dissection of the UPR in diverse cell types, tissues, and organisms.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"29 1","pages":"111067"},"PeriodicalIF":4.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.jbc.2025.110956
Thomas Neill, Carolyn G Chen, Simone Buraschi, Renato V Iozzo
{"title":"Catabolic degradation of endothelial VEGFA via autophagy.","authors":"Thomas Neill, Carolyn G Chen, Simone Buraschi, Renato V Iozzo","doi":"10.1016/j.jbc.2025.110956","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110956","url":null,"abstract":"","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"302 1","pages":"110956"},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.jbc.2025.111060
Fabian M B Thöne,Maya M Polovitskaya,Uta E Höpken,Armin Rehm,Thomas J Jentsch
The volume-regulated anion channel VRAC is a hetero-hexamer composed of LRRC8A and any of the four other LRRC8 paralogs (LRRC8B-E). Depending on their subunit composition, VRACs not only transport chloride, but also a range of organic substrates including 2'3'-cGAMP (cGAMP). Transfer of this immunomodulator from tumor to host cells is critical for anti-tumor immunity. Whether this process depends on VRAC in vivo remains incompletely understood. To address this issue, we studied subcutaneous MC38 and B16-F10 tumors in syngeneic mice. Enhanced growth of MC38 tumors lacking cGAMP production confirmed the importance of tumor-produced cGAMP. The impact of VRAC-mediated cGAMP-efflux from tumor cells and its uptake into cells of the tumor microenvironment was investigated using LRRC8A-deficient tumor cells and recipient mice with selective LRRC8 subunit disruptions, respectively. Changed serum cytokines indicated moderate immunomodulatory effects of VRAC-mediated cGAMP export from MC38 tumors. However, tumor growth and the cGAMP-mediated anti-tumor immune response were independent of both, tumor- and host-expressed VRAC. Disruption of any of the non-essential subunits, LRRC8B-LRRC8E, had no discernible effect on T or B cell development in mice. Whereas tumor-produced cGAMP markedly suppresses tumor growth, transport of this immunomodulator to the tumor environment primarily involves transporters distinct from VRAC.
{"title":"A protective cGAMP-mediated anti-tumor immune response can proceed without LRRC8/VRAC channels.","authors":"Fabian M B Thöne,Maya M Polovitskaya,Uta E Höpken,Armin Rehm,Thomas J Jentsch","doi":"10.1016/j.jbc.2025.111060","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.111060","url":null,"abstract":"The volume-regulated anion channel VRAC is a hetero-hexamer composed of LRRC8A and any of the four other LRRC8 paralogs (LRRC8B-E). Depending on their subunit composition, VRACs not only transport chloride, but also a range of organic substrates including 2'3'-cGAMP (cGAMP). Transfer of this immunomodulator from tumor to host cells is critical for anti-tumor immunity. Whether this process depends on VRAC in vivo remains incompletely understood. To address this issue, we studied subcutaneous MC38 and B16-F10 tumors in syngeneic mice. Enhanced growth of MC38 tumors lacking cGAMP production confirmed the importance of tumor-produced cGAMP. The impact of VRAC-mediated cGAMP-efflux from tumor cells and its uptake into cells of the tumor microenvironment was investigated using LRRC8A-deficient tumor cells and recipient mice with selective LRRC8 subunit disruptions, respectively. Changed serum cytokines indicated moderate immunomodulatory effects of VRAC-mediated cGAMP export from MC38 tumors. However, tumor growth and the cGAMP-mediated anti-tumor immune response were independent of both, tumor- and host-expressed VRAC. Disruption of any of the non-essential subunits, LRRC8B-LRRC8E, had no discernible effect on T or B cell development in mice. Whereas tumor-produced cGAMP markedly suppresses tumor growth, transport of this immunomodulator to the tumor environment primarily involves transporters distinct from VRAC.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"287 1","pages":"111060"},"PeriodicalIF":4.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
COX6B1 is a nuclear-encoded subunit of the human mitochondrial cytochrome c oxidase (cIV) located in its intermembrane space-facing region. The relevance of COX6B1 in mitochondrial physiopathology was highlighted by the missense pathogenic variants associated with cIV deficiency. Despite the assigned COX6B1 role as a late incorporation subunit, the COX6B1 human cell line knock-out (KO) exhibited a total loss of cIV. To get a deeper insight into the mechanisms driving the lack of cIV assembly or destabilization in the absence of COX6B1, we used the COX6B1 KO cell background to express alternative oxidase and COX6B1 pathogenic variants. These analyses uncovered that the COX6B1 subunit is indispensable for redox-sensitive early cIV assembly steps, besides its contribution to the stabilization of cIV in the late assembly stages. In addition, we have evidenced the incorporation of partially assembled cIV modules directly into supercomplex structures, supporting the 'cooperative assembly' model for respiratory chain biogenesis.
{"title":"The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.","authors":"Kristýna Čunátová,Marek Vrbacký,Michal Knězů,Alena Pecinová,Lukáš Alán,Josef Houštěk,Erika Fernández-Vizarra,Tomáš Mráček,Petr Pecina","doi":"10.1016/j.jbc.2025.111070","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.111070","url":null,"abstract":"COX6B1 is a nuclear-encoded subunit of the human mitochondrial cytochrome c oxidase (cIV) located in its intermembrane space-facing region. The relevance of COX6B1 in mitochondrial physiopathology was highlighted by the missense pathogenic variants associated with cIV deficiency. Despite the assigned COX6B1 role as a late incorporation subunit, the COX6B1 human cell line knock-out (KO) exhibited a total loss of cIV. To get a deeper insight into the mechanisms driving the lack of cIV assembly or destabilization in the absence of COX6B1, we used the COX6B1 KO cell background to express alternative oxidase and COX6B1 pathogenic variants. These analyses uncovered that the COX6B1 subunit is indispensable for redox-sensitive early cIV assembly steps, besides its contribution to the stabilization of cIV in the late assembly stages. In addition, we have evidenced the incorporation of partially assembled cIV modules directly into supercomplex structures, supporting the 'cooperative assembly' model for respiratory chain biogenesis.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"7 1","pages":"111070"},"PeriodicalIF":4.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.jbc.2025.111066
Qi Cao,Yuqing Wang,Yuange Duan
Functional adenosine-to-inosine (A-to-I) mRNA editing sites are continuously identified in cellular organisms. Despite that several editing sites have been linked to various human cancers, the dynamic RNA editing in the progression of myeloid neoplasms remains less known, preventing a clearer understanding of the functional repertoire of RNA editing in blood diseases. By analyzing transcriptomes from healthy controls (HC), low-risk myelodysplastic syndrome (MDS), high-risk MDS, and acute myeloid leukemia (AML), we reveal widespread and dynamic RNA editing events accompanying disease progression. Immunoglobulin genes are enriched for nonsynonymous editing sites with significantly altered editing levels in myeloid neoplasms, and such recoding sites often show genomic substitutions to hardwired G during mammalian evolution. Collectively, our findings broaden the functional spectrum of RNA editing in human and highlight its potential as a driver, responsor, or biomarker of myeloid neoplasms, underscoring its significance in human disease evolution.
{"title":"Dynamic and extensive A-to-I RNA recoding in immunoglobulin shapes myeloid neoplasms transcriptome.","authors":"Qi Cao,Yuqing Wang,Yuange Duan","doi":"10.1016/j.jbc.2025.111066","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.111066","url":null,"abstract":"Functional adenosine-to-inosine (A-to-I) mRNA editing sites are continuously identified in cellular organisms. Despite that several editing sites have been linked to various human cancers, the dynamic RNA editing in the progression of myeloid neoplasms remains less known, preventing a clearer understanding of the functional repertoire of RNA editing in blood diseases. By analyzing transcriptomes from healthy controls (HC), low-risk myelodysplastic syndrome (MDS), high-risk MDS, and acute myeloid leukemia (AML), we reveal widespread and dynamic RNA editing events accompanying disease progression. Immunoglobulin genes are enriched for nonsynonymous editing sites with significantly altered editing levels in myeloid neoplasms, and such recoding sites often show genomic substitutions to hardwired G during mammalian evolution. Collectively, our findings broaden the functional spectrum of RNA editing in human and highlight its potential as a driver, responsor, or biomarker of myeloid neoplasms, underscoring its significance in human disease evolution.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"7 1","pages":"111066"},"PeriodicalIF":4.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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