{"title":"Emerging roles of RNA N4-acetylcytidine modification in reproductive health.","authors":"Zibaguli Wubulikasimu, Hongyu Zhao, Fengbiao Mao, Xiaolu Zhao","doi":"10.1093/procel/pwaf013","DOIUrl":"10.1093/procel/pwaf013","url":null,"abstract":"<p><p>N4-acetylcytidine (ac4C), an emerging posttranscriptional RNA modification, plays a pivotal role in epigenetic regulation. Ac4C is detected not only in tRNA, rRNA, and mRNA, but also in miRNA, lncRNA, viral RNA, and even DNA. Functionally, ac4C stabilizes mRNA, enhances protein translation fidelity, and impacts various biological processes and diseases such as cancer, inflammation, immune regulation, neural diseases, osteogenic differentiation, cardiovascular diseases, viral infections, and replication. Current research primarily focuses on ac4C's roles in cancer progression and immunity, with emerging findings in gynecological diseases and reproduction. However, a comprehensive understanding of ac4C's implications in reproductive health is lacking. This review provides a historical perspective on ac4C's discovery and detection methods, elucidates its functions in reproductive development and gynecological disorders, and offers insights for further research in reproductive health. This review aims to pave the way for innovative therapeutic approaches and precise diagnostic tools tailored to this field.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"458-477"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450208","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}
Protein & CellPub Date : 2025-06-20DOI: 10.1093/procel/pwaf010
Xiaolei Zhang, Ruimin Xu, Yuyan Zhao, Yijia Yang, Qi Shi, Hong Wang, Xiaoyu Liu, Shaorong Gao, Chong Li
{"title":"Setd2 overexpression rescues bivalent gene expression during SCNT-mediated ZGA.","authors":"Xiaolei Zhang, Ruimin Xu, Yuyan Zhao, Yijia Yang, Qi Shi, Hong Wang, Xiaoyu Liu, Shaorong Gao, Chong Li","doi":"10.1093/procel/pwaf010","DOIUrl":"10.1093/procel/pwaf010","url":null,"abstract":"<p><p>Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"439-457"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410165","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}
Protein & CellPub Date : 2025-06-20DOI: 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":"391-417"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","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}
Protein & CellPub Date : 2025-06-20DOI: 10.1093/procel/pwae063
Xue Zhang, Jing Han, Yudong Wang, Li Feng, Zhisong Fan, Yu Su, Wenya Song, Lan Wang, Long Wang, Hui Jin, Jiayin Liu, Dan Li, Guiying Li, Yan Liu, Jing Zuo, Zhiyu Ni
{"title":"Microbiome, metabolome, and transcriptome analyses in esophageal squamous cell carcinoma: insights into immune modulation by F. nucleatum.","authors":"Xue Zhang, Jing Han, Yudong Wang, Li Feng, Zhisong Fan, Yu Su, Wenya Song, Lan Wang, Long Wang, Hui Jin, Jiayin Liu, Dan Li, Guiying Li, Yan Liu, Jing Zuo, Zhiyu Ni","doi":"10.1093/procel/pwae063","DOIUrl":"10.1093/procel/pwae063","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"491-496"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547022","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}
Protein & CellPub Date : 2025-06-12DOI: 10.1093/procel/pwaf047
Haoxian Zhou, Shu Wu, Bin Li, Rongjinlei Zhang, Ying Zou, Mibu Cao, Anhua Xu, Kewei Zheng, Qinghua Zhou, Jia Wang, Jinping Zheng, Jianhua Yang, Yuanlong Ge, Zhanyi Lin, Zhenyu Ju
{"title":"RNA G-quadruplex (rG4) exacerbates cellular senescence by mediating ribosome pausing.","authors":"Haoxian Zhou, Shu Wu, Bin Li, Rongjinlei Zhang, Ying Zou, Mibu Cao, Anhua Xu, Kewei Zheng, Qinghua Zhou, Jia Wang, Jinping Zheng, Jianhua Yang, Yuanlong Ge, Zhanyi Lin, Zhenyu Ju","doi":"10.1093/procel/pwaf047","DOIUrl":"https://doi.org/10.1093/procel/pwaf047","url":null,"abstract":"<p><p>Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated rG4 structures within coding sequence (CDS) can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275833","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}
Protein & CellPub Date : 2025-06-11DOI: 10.1093/procel/pwaf016
Mingkang Jia, Gan Zhao, Mengjie Sun, Xiangyang Wang, He Ren, Guangwei Xin, Qing Jiang, Chuanmao Zhang
{"title":"Lamin C conserves DNA replication factors via phase separation during oxidative stress for DNA replication recovery.","authors":"Mingkang Jia, Gan Zhao, Mengjie Sun, Xiangyang Wang, He Ren, Guangwei Xin, Qing Jiang, Chuanmao Zhang","doi":"10.1093/procel/pwaf016","DOIUrl":"https://doi.org/10.1093/procel/pwaf016","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275832","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}
Protein & CellPub Date : 2025-06-10DOI: 10.1093/procel/pwaf042
Yuting Ma, Juan Zhang, Hankui Liu, Dingfeng Li, Sicheng Guo, Jialuo Han, Lei Wang, Shaojun Yu, Xi Su, Yongchang Gao, Xiumei Lin, A San, Yushan Peng, Guibo Li, Hui Jiang, Wei Wang, Huanming Yang, Jian Wang, Shida Zhu, Lijian Zhao, Jianguo Zhang, Qiang Liu
{"title":"Spatiotemporal characterization of disease-associated neurons in the entorhinal cortex-hippocampal circuit during AD progression.","authors":"Yuting Ma, Juan Zhang, Hankui Liu, Dingfeng Li, Sicheng Guo, Jialuo Han, Lei Wang, Shaojun Yu, Xi Su, Yongchang Gao, Xiumei Lin, A San, Yushan Peng, Guibo Li, Hui Jiang, Wei Wang, Huanming Yang, Jian Wang, Shida Zhu, Lijian Zhao, Jianguo Zhang, Qiang Liu","doi":"10.1093/procel/pwaf042","DOIUrl":"https://doi.org/10.1093/procel/pwaf042","url":null,"abstract":"<p><p>The entorhinal cortex (EC)-hippocampal (HPC) circuit is particularly vulnerable to Alzheimer's disease (AD) pathology, yet the underlying molecular mechanisms remain unclear. By employing the high-depth sequencing strategy Smart-seq2, we tracked gene expression changes across various neuron types within this circuit at different stages of AD pathology. We observed a decrease in the extent of gene expression changes in AD versus wild-type (WT) mice as the disease advanced. Functionally, we demonstrate that both mitochondrial and ribosomal pathways were increasingly activated, while neuronal pathways were inhibited with AD progression. Our findings indicate that the reduction of EC-stellate cells disrupts Meg3-mediated energy metabolism, contributing to energy dysfunction in AD. Additionally, we identified GFAP-positive neurons as a distinct population of disease-associated neurons, exhibiting a loss of neuronal-like characteristics, alongside the emergence of glia- and stem-like features. The number of GFAP-positive neurons increased with AD progression, a trend consistently observed in both AD model mice and AD patients. In summary, this study identifies and characterizes GFAP-positive neurons as a novel subtype of disease-associated neurons in AD pathology, providing insights into their potential role in disease progression.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258876","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}