Cell ResearchPub Date : 2025-02-06DOI: 10.1038/s41422-025-01079-7
Rebecca T. Chu, Adam B. Schroer, Saul A. Villeda
{"title":"Halt aging? — functional HSCs lead the way","authors":"Rebecca T. Chu, Adam B. Schroer, Saul A. Villeda","doi":"10.1038/s41422-025-01079-7","DOIUrl":"10.1038/s41422-025-01079-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 3","pages":"157-158"},"PeriodicalIF":28.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-025-01079-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192310","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}
Cell ResearchPub Date : 2025-01-29DOI: 10.1038/s41422-025-01078-8
Ling-Qi Xie, Biao Hu, Ren-Bin Lu, Ya-Lun Cheng, Xin Chen, Jie Wen, Yao Xiao, Yu-Ze An, Ning Peng, Yu Dai, Genqing Xie, Qi Guo, Hui Peng, Xiang-Hang Luo
{"title":"Raptin, a sleep-induced hypothalamic hormone, suppresses appetite and obesity","authors":"Ling-Qi Xie, Biao Hu, Ren-Bin Lu, Ya-Lun Cheng, Xin Chen, Jie Wen, Yao Xiao, Yu-Ze An, Ning Peng, Yu Dai, Genqing Xie, Qi Guo, Hui Peng, Xiang-Hang Luo","doi":"10.1038/s41422-025-01078-8","DOIUrl":"10.1038/s41422-025-01078-8","url":null,"abstract":"Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 3","pages":"165-185"},"PeriodicalIF":28.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-025-01078-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055050","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}
Cell ResearchPub Date : 2025-01-20DOI: 10.1038/s41422-024-01070-8
Hao Wu, Chu-Xiao Liu, Ling-Ling Chen
{"title":"Beyond housekeeping: a new role of snoRNA in nascent protein secretion","authors":"Hao Wu, Chu-Xiao Liu, Ling-Ling Chen","doi":"10.1038/s41422-024-01070-8","DOIUrl":"https://doi.org/10.1038/s41422-024-01070-8","url":null,"abstract":"<p><b>Although small nucleolar RNAs (snoRNAs) are well-known for guiding 2′-</b><b><i>O</i></b><b>-methylation and pseudouridine modification on ribosomal RNAs and small nuclear RNAs, their additional functions have remained largely undefined. Liu and colleagues developed snoKARR-seq to map transcriptome-wide snoRNA targets, and discovered an unexpected role of snoRNA:</b> <b><i>SNORA73</i></b> <b>simultaneously binds to the target mRNA and the</b> <b><i>7SL</i></b> <b>RNA of the signal recognition particle to form ternary interactions that facilitate the secretion of the encoded protein</b>.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"101 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990077","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}
Cell ResearchPub Date : 2025-01-17DOI: 10.1038/s41422-025-01074-y
Han Wang, Shi-Min Zhao
{"title":"Metabolite is a part of immune-regulating circuit","authors":"Han Wang, Shi-Min Zhao","doi":"10.1038/s41422-025-01074-y","DOIUrl":"10.1038/s41422-025-01074-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 3","pages":"159-160"},"PeriodicalIF":28.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-025-01074-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000744","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}
Cell ResearchPub Date : 2025-01-15DOI: 10.1038/s41422-025-01072-0
Blake A. Fordyce, Bryan L. Roth
{"title":"Chemogenetics for sensing antigens","authors":"Blake A. Fordyce, Bryan L. Roth","doi":"10.1038/s41422-025-01072-0","DOIUrl":"https://doi.org/10.1038/s41422-025-01072-0","url":null,"abstract":"<p><b>Antigen-based systems offer highly specific binding and customizability, broadening their application to various fields of cell biology. In a recent issue of</b> <b><i>Nature</i></b><b>, Kalogriopoulos et al. design antigen-sensing G-protein-coupled receptors that exhibit programmable responses spanning exogenous gene expression, G-protein signaling, and receptor activation</b>.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"337 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981352","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}
Cell ResearchPub Date : 2025-01-14DOI: 10.1038/s41422-024-01058-4
Haicheng Liao, Yu Fang, Junjie Yin, Min He, Yingjie Wei, Juan Zhang, Shuang Yong, Jiankui Cha, Li Song, Xiaobo Zhu, Xixi Chen, Ján Kováč, Qingqing Hou, Zhaotang Ma, Xiaogang Zhou, Lin Chen, Emi Yumoto, Tian Yang, Qi He, Wei Li, Yixin Deng, Haoxuan Li, Mingwu Li, Hai Qing, Lijuan Zou, Yu Bi, Jiali Liu, Yihua Yang, Daihua Ye, Qi Tao, Long Wang, Qing Xiong, Xiang Lu, Yongyan Tang, Ting Li, Bingtian Ma, Peng Qin, Yan Li, Wenming Wang, Yangwen Qian, Jaroslav Ďurkovič, Koji Miyamoto, Mawsheng Chern, Shigui Li, Weitao Li, Jing Wang, Xuewei Chen
{"title":"Rice transcription factor bHLH25 confers resistance to multiple diseases by sensing H2O2","authors":"Haicheng Liao, Yu Fang, Junjie Yin, Min He, Yingjie Wei, Juan Zhang, Shuang Yong, Jiankui Cha, Li Song, Xiaobo Zhu, Xixi Chen, Ján Kováč, Qingqing Hou, Zhaotang Ma, Xiaogang Zhou, Lin Chen, Emi Yumoto, Tian Yang, Qi He, Wei Li, Yixin Deng, Haoxuan Li, Mingwu Li, Hai Qing, Lijuan Zou, Yu Bi, Jiali Liu, Yihua Yang, Daihua Ye, Qi Tao, Long Wang, Qing Xiong, Xiang Lu, Yongyan Tang, Ting Li, Bingtian Ma, Peng Qin, Yan Li, Wenming Wang, Yangwen Qian, Jaroslav Ďurkovič, Koji Miyamoto, Mawsheng Chern, Shigui Li, Weitao Li, Jing Wang, Xuewei Chen","doi":"10.1038/s41422-024-01058-4","DOIUrl":"10.1038/s41422-024-01058-4","url":null,"abstract":"Hydrogen peroxide (H2O2) is a ubiquitous signal regulating many biological processes, including innate immunity, in all eukaryotes. However, it remains largely unknown that how transcription factors directly sense H2O2 in eukaryotes. Here, we report that rice basic/helix-loop-helix transcription factor bHLH25 directly senses H2O2 to confer resistance to multiple diseases caused by fungi or bacteria. Upon pathogen attack, rice plants increase the production of H2O2, which directly oxidizes bHLH25 at methionine 256 in the nucleus. Oxidized bHLH25 represses miR397b expression to activate lignin biosynthesis for plant cell wall reinforcement, preventing pathogens from penetrating plant cells. Lignin biosynthesis consumes H2O2 causing accumulation of non-oxidized bHLH25. Non-oxidized bHLH25 switches to promote the expression of Copalyl Diphosphate Synthase 2 (CPS2), which increases phytoalexin biosynthesis to inhibit expansion of pathogens that escape into plants. This oxidization/non-oxidation status change of bHLH25 allows plants to maintain H2O2, lignin and phytoalexin at optimized levels to effectively fight against pathogens and prevents these three molecules from over-accumulation that harms plants. Thus, our discovery reveals a novel mechanism by which a single protein promotes two independent defense pathways against pathogens. Importantly, the bHLH25 orthologues from available plant genomes all contain a conserved M256-like methionine suggesting the broad existence of this mechanism in the plant kingdom. Moreover, this Met-oxidation mechanism may also be employed by other eukaryotic transcription factors to sense H2O2 to change functions.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 3","pages":"205-219"},"PeriodicalIF":28.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01058-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974548","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}
Cell ResearchPub Date : 2025-01-14DOI: 10.1038/s41422-024-01069-1
Jorge Ruiz-Orera, Norbert Hübner
{"title":"The non-canonical proteome: a novel contributor to cancer proliferation","authors":"Jorge Ruiz-Orera, Norbert Hübner","doi":"10.1038/s41422-024-01069-1","DOIUrl":"10.1038/s41422-024-01069-1","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 3","pages":"155-156"},"PeriodicalIF":28.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01069-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974546","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}
{"title":"Comprehensive discovery and functional characterization of the noncanonical proteome","authors":"Chengyu Shi, Fangzhou Liu, Xinwan Su, Zuozhen Yang, Ying Wang, Shanshan Xie, Shaofang Xie, Qiang Sun, Yu Chen, Lingjie Sang, Manman Tan, Linyu Zhu, Kai Lei, Junhong Li, Jiecheng Yang, Zerui Gao, Meng Yu, Xinyi Wang, Junfeng Wang, Jing Chen, Wei Zhuo, Zhaoyuan Fang, Jian Liu, Qingfeng Yan, Dante Neculai, Qiming Sun, Jianzhong Shao, Weiqiang Lin, Wei Liu, Jian Chen, Liangjing Wang, Yang Liu, Xu Li, Tianhua Zhou, Aifu Lin","doi":"10.1038/s41422-024-01059-3","DOIUrl":"10.1038/s41422-024-01059-3","url":null,"abstract":"The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs. Moreover, our CRISPR screening revealed that 1161 peptides are involved in tumor cell proliferation. The presence and physiological function of a subset of these peptides, selected based on screening scores, amino acid length, and various indicators, were verified through Flag-knockin and multiple other methods. To further characterize the potential regulatory mechanisms involved, we constructed a framework based on artificial intelligence structure prediction and peptide‒protein interaction network analysis for the top 100 candidates and revealed that these cancer-related peptides have diverse subcellular locations and participate in organelle-specific processes. Further investigation verified the interacting partners of pep1-nc-OLMALINC, pep5-nc-TRHDE-AS1, pep-nc-ZNF436-AS1 and pep2-nc-AC027045.3, and the functions of these peptides in mitochondrial complex assembly, energy metabolism, and cholesterol metabolism, respectively. We showed that pep5-nc-TRHDE-AS1 and pep2-nc-AC027045.3 had substantial impacts on tumor growth in xenograft models. Furthermore, the dysregulation of these four peptides is closely correlated with clinical prognosis. Taken together, our study provides a comprehensive characterization of the noncanonical proteome, and highlights critical roles of these previously unannotated peptides in cancer biology.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 3","pages":"186-204"},"PeriodicalIF":28.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01059-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964139","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}