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Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia. 巨噬细胞通过 NLRP3 信号通路分泌的 Lcn2 可诱发重症肺炎。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-24 DOI: 10.1093/procel/pwae045
Mingya Liu, Feifei Qi, Jue Wang, Fengdi Li, Qi Lv, Ran Deng, Xujian Liang, Shasha Zhou, Pin Yu, Yanfeng Xu, Yaqing Zhang, Yiwei Yan, Ming Liu, Shuyue Li, Guocui Mou, Linlin Bao
{"title":"Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia.","authors":"Mingya Liu, Feifei Qi, Jue Wang, Fengdi Li, Qi Lv, Ran Deng, Xujian Liang, Shasha Zhou, Pin Yu, Yanfeng Xu, Yaqing Zhang, Yiwei Yan, Ming Liu, Shuyue Li, Guocui Mou, Linlin Bao","doi":"10.1093/procel/pwae045","DOIUrl":"https://doi.org/10.1093/procel/pwae045","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047110","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
Adenosine-to-Inosine RNA editing in cancer: molecular mechanisms and downstream targets. 癌症中的腺苷转肌苷 RNA 编辑:分子机制和下游靶点。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-10 DOI: 10.1093/procel/pwae039
Hao Cheng, Jun Yu, Chi Chun Wong
{"title":"Adenosine-to-Inosine RNA editing in cancer: molecular mechanisms and downstream targets.","authors":"Hao Cheng, Jun Yu, Chi Chun Wong","doi":"10.1093/procel/pwae039","DOIUrl":"10.1093/procel/pwae039","url":null,"abstract":"<p><p>Adenosine-to-Inosine (A-to-I), one of the most prevalent RNA modifications, has recently garnered significant attention. The A-to-I modification actively contributes to biological and pathological processes by affecting the structure and function of various RNA molecules, including double stranded RNA, transfer RNA, microRNA, and viral RNA. Increasing evidence suggests that A-to-I plays a crucial role in the development of human disease, particularly in cancer, and aberrant A-to-I levels are closely associated with tumorigenesis and progression through regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of A-to-I modification in cancer are not comprehensively understood. Here, we review the latest advances regarding the A-to-I editing pathways implicated in cancer, describing their biological functions and their connections to the disease.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913755","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
Advances in Gene and Cellular Therapeutic Approaches for Huntington's Disease. 亨廷顿氏症基因和细胞治疗方法的进展。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-09 DOI: 10.1093/procel/pwae042
Xuejiao Piao, Dan Li, Hui Liu, Qing Guo, Yang Yu
{"title":"Advances in Gene and Cellular Therapeutic Approaches for Huntington's Disease.","authors":"Xuejiao Piao, Dan Li, Hui Liu, Qing Guo, Yang Yu","doi":"10.1093/procel/pwae042","DOIUrl":"https://doi.org/10.1093/procel/pwae042","url":null,"abstract":"<p><p>Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and non-pharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910099","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
Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens. 磷脂酰肌醇-4,5-二磷酸的内分解代谢是建立抵御病原体能力的基础。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-08-01 DOI: 10.1093/procel/pwae041
Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi
{"title":"Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.","authors":"Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi","doi":"10.1093/procel/pwae041","DOIUrl":"https://doi.org/10.1093/procel/pwae041","url":null,"abstract":"<p><p>Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of C. elegans with P. aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal PI(4,5)P2 and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity, and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860723","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
Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues. 衰老猕猴眼球流出组织的单细胞转录组图谱。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-07-20 DOI: 10.1093/procel/pwad067
Jian Wu, Chaoye Wang, Shuhui Sun, Tianmin Ren, Lijie Pan, Hongyi Liu, Simeng Hou, Shen Wu, Xuejing Yan, Jingxue Zhang, Xiaofang Zhao, Weihai Liu, Sirui Zhu, Shuwen Wei, Chi Zhang, Xu Jia, Qi Zhang, Ziyu Yu, Yehong Zhuo, Qi Zhao, Chenlong Yang, Ningli Wang
{"title":"Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues.","authors":"Jian Wu, Chaoye Wang, Shuhui Sun, Tianmin Ren, Lijie Pan, Hongyi Liu, Simeng Hou, Shen Wu, Xuejing Yan, Jingxue Zhang, Xiaofang Zhao, Weihai Liu, Sirui Zhu, Shuwen Wei, Chi Zhang, Xu Jia, Qi Zhang, Ziyu Yu, Yehong Zhuo, Qi Zhao, Chenlong Yang, Ningli Wang","doi":"10.1093/procel/pwad067","DOIUrl":"10.1093/procel/pwad067","url":null,"abstract":"<p><p>The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in-depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"594-611"},"PeriodicalIF":13.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747301","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
Skeletal stem cells in bone development, homeostasis, and disease. 骨骼干细胞在骨骼发育、平衡和疾病中的作用。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-07-20 DOI: 10.1093/procel/pwae008
Guixin Yuan, Xixi Lin, Ying Liu, Matthew B Greenblatt, Ren Xu
{"title":"Skeletal stem cells in bone development, homeostasis, and disease.","authors":"Guixin Yuan, Xixi Lin, Ying Liu, Matthew B Greenblatt, Ren Xu","doi":"10.1093/procel/pwae008","DOIUrl":"10.1093/procel/pwae008","url":null,"abstract":"<p><p>Tissue-resident stem cells are essential for development and repair, and in the skeleton, this function is fulfilled by recently identified skeletal stem cells (SSCs). However, recent work has identified that SSCs are not monolithic, with long bones, craniofacial sites, and the spine being formed by distinct stem cells. Recent studies have utilized techniques such as fluorescence-activated cell sorting, lineage tracing, and single-cell sequencing to investigate the involvement of SSCs in bone development, homeostasis, and disease. These investigations have allowed researchers to map the lineage commitment trajectory of SSCs in different parts of the body and at different time points. Furthermore, recent studies have shed light on the characteristics of SSCs in both physiological and pathological conditions. This review focuses on discussing the spatiotemporal distribution of SSCs and enhancing our understanding of the diversity and plasticity of SSCs by summarizing recent discoveries.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"559-574"},"PeriodicalIF":13.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040217","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
DNA methylation clocks for estimating biological age in Chinese cohorts. 用于估算中国人群生物年龄的 DNA 甲基化时钟。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-07-20 DOI: 10.1093/procel/pwae011
Zikai Zheng, Jiaming Li, Tianzi Liu, Yanling Fan, Qiao-Cheng Zhai, Muzhao Xiong, Qiao-Ran Wang, Xiaoyan Sun, Qi-Wen Zheng, Shanshan Che, Beier Jiang, Quan Zheng, Cui Wang, Lixiao Liu, Jiale Ping, Si Wang, Dan-Dan Gao, Jinlin Ye, Kuan Yang, Yuesheng Zuo, Shuai Ma, Yun-Gui Yang, Jing Qu, Feng Zhang, Peilin Jia, Guang-Hui Liu, Weiqi Zhang
{"title":"DNA methylation clocks for estimating biological age in Chinese cohorts.","authors":"Zikai Zheng, Jiaming Li, Tianzi Liu, Yanling Fan, Qiao-Cheng Zhai, Muzhao Xiong, Qiao-Ran Wang, Xiaoyan Sun, Qi-Wen Zheng, Shanshan Che, Beier Jiang, Quan Zheng, Cui Wang, Lixiao Liu, Jiale Ping, Si Wang, Dan-Dan Gao, Jinlin Ye, Kuan Yang, Yuesheng Zuo, Shuai Ma, Yun-Gui Yang, Jing Qu, Feng Zhang, Peilin Jia, Guang-Hui Liu, Weiqi Zhang","doi":"10.1093/procel/pwae011","DOIUrl":"10.1093/procel/pwae011","url":null,"abstract":"<p><p>Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation (DNAm) at specific CpG sites. However, a systematic comparison between DNA methylation data and other omics datasets has not yet been performed. Moreover, available DNAm age predictors are based on datasets with limited ethnic representation. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing the basis for evaluating aging intervention strategies.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"575-593"},"PeriodicalIF":13.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120442","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
Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics. 通过整合单细胞 RNA 测序和空间转录组学,解密人类子宫腺肌病的综合转录图谱。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-07-01 DOI: 10.1093/procel/pwae012
Tao Chen, Yiliang Xu, Xiaocui Xu, Jianzhang Wang, Zhiruo Qiu, Yayuan Yu, Xiaohong Jiang, Wanqi Shao, Dandan Bai, Mingzhu Wang, Shuyan Mei, Tao Cheng, Li Wu, Shaorong Gao, Xuan Che
{"title":"Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics.","authors":"Tao Chen, Yiliang Xu, Xiaocui Xu, Jianzhang Wang, Zhiruo Qiu, Yayuan Yu, Xiaohong Jiang, Wanqi Shao, Dandan Bai, Mingzhu Wang, Shuyan Mei, Tao Cheng, Li Wu, Shaorong Gao, Xuan Che","doi":"10.1093/procel/pwae012","DOIUrl":"10.1093/procel/pwae012","url":null,"abstract":"<p><p>Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding \"invagination\" and \"metaplasia\" theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial (LGR5+) and invasive stromal (PKIB+) subpopulations, along with WFDC1+ progenitor cells, supporting a complex interplay between \"invagination\" and \"metaplasia\" theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving pleiotrophin, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"530-546"},"PeriodicalIF":13.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132465","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
Long way up: rethink diseases in light of phase separation and phase transition. 长路漫漫:从相分离和相转变的角度重新思考疾病。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-07-01 DOI: 10.1093/procel/pwad057
Mingrui Ding, Weifan Xu, Gaofeng Pei, Pilong Li
{"title":"Long way up: rethink diseases in light of phase separation and phase transition.","authors":"Mingrui Ding, Weifan Xu, Gaofeng Pei, Pilong Li","doi":"10.1093/procel/pwad057","DOIUrl":"10.1093/procel/pwad057","url":null,"abstract":"<p><p>Biomolecular condensation, driven by multivalency, serves as a fundamental mechanism within cells, facilitating the formation of distinct compartments, including membraneless organelles that play essential roles in various cellular processes. Perturbations in the delicate equilibrium of condensation, whether resulting in gain or loss of phase separation, have robustly been associated with cellular dysfunction and physiological disorders. As ongoing research endeavors wholeheartedly embrace this newly acknowledged principle, a transformative shift is occurring in our comprehension of disease. Consequently, significant strides have been made in unraveling the profound relevance and potential causal connections between abnormal phase separation and various diseases. This comprehensive review presents compelling recent evidence that highlight the intricate associations between aberrant phase separation and neurodegenerative diseases, cancers, and infectious diseases. Additionally, we provide a succinct summary of current efforts and propose innovative solutions for the development of potential therapeutics to combat the pathological consequences attributed to aberrant phase separation.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"475-492"},"PeriodicalIF":13.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807229","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
ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader. ILF3作为端粒r环读取器保护端粒免受异常同源重组。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2024-07-01 DOI: 10.1093/procel/pwad054
Chuanle Wang, Yan Huang, Yue Yang, Ruofei Li, Yingying Li, Hongxin Qiu, Jiali Wu, Guang Shi, Wenbin Ma, Zhou Songyang
{"title":"ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.","authors":"Chuanle Wang, Yan Huang, Yue Yang, Ruofei Li, Yingying Li, Hongxin Qiu, Jiali Wu, Guang Shi, Wenbin Ma, Zhou Songyang","doi":"10.1093/procel/pwad054","DOIUrl":"10.1093/procel/pwad054","url":null,"abstract":"<p><p>Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway. Dysregulated R-loops can cause stalled replication forks and telomere instability. However, how R-loops are recognized and regulated, particularly at telomeres, is not well understood. We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination. Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses. In addition, ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway. Using the proximity-dependent biotin identification (BioID) technology, we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases, including DHX9. Importantly, ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9. Our findings suggest that ILF3 may function as a reader of telomeric R-loops, helping to prevent abnormal homologous recombination and maintain telomere homeostasis.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"493-511"},"PeriodicalIF":13.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291677","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
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