Zihong Kang, Ruimeng Li, Chang Liu, Xiaozhe Dong, Yuxuan Hu, Lei Xu, Xinyu Liu, Yunfan Xiang, Liming Gao, Wenzhe Si, Lei Wang, Qing Li, Liang Zhang, Huan Wang, Xuerui Yang, Jun Liu
{"title":"m6A 修饰的 cenRNA 可稳定 CENPA,确保癌细胞中心粒的完整性","authors":"Zihong Kang, Ruimeng Li, Chang Liu, Xiaozhe Dong, Yuxuan Hu, Lei Xu, Xinyu Liu, Yunfan Xiang, Liming Gao, Wenzhe Si, Lei Wang, Qing Li, Liang Zhang, Huan Wang, Xuerui Yang, Jun Liu","doi":"10.1016/j.cell.2024.08.040","DOIUrl":null,"url":null,"abstract":"<p>m<sup>6</sup>A modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of m<sup>6</sup>A modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an m<sup>6</sup>A reader of cenRNA. CENPA is localized at centromeres and is essential in preserving centromere integrity and function during mitosis. The m<sup>6</sup>A-modified cenRNA stabilizes centromeric localization of CENPA in cancer cells during the S phase of the cell cycle. Mutations of CENPA at the Leu61 and the Arg63 or removal of cenRNA m<sup>6</sup>A modification lead to loss of centromere-bound CENPA during S phase. This in turn results in compromised centromere integrity and abnormal chromosome separation and hinders cancer cell proliferation and tumor growth. Our findings unveil an m<sup>6</sup>A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potential targets for cancer therapy.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":null,"pages":null},"PeriodicalIF":45.5000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells\",\"authors\":\"Zihong Kang, Ruimeng Li, Chang Liu, Xiaozhe Dong, Yuxuan Hu, Lei Xu, Xinyu Liu, Yunfan Xiang, Liming Gao, Wenzhe Si, Lei Wang, Qing Li, Liang Zhang, Huan Wang, Xuerui Yang, Jun Liu\",\"doi\":\"10.1016/j.cell.2024.08.040\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>m<sup>6</sup>A modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of m<sup>6</sup>A modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an m<sup>6</sup>A reader of cenRNA. CENPA is localized at centromeres and is essential in preserving centromere integrity and function during mitosis. The m<sup>6</sup>A-modified cenRNA stabilizes centromeric localization of CENPA in cancer cells during the S phase of the cell cycle. Mutations of CENPA at the Leu61 and the Arg63 or removal of cenRNA m<sup>6</sup>A modification lead to loss of centromere-bound CENPA during S phase. This in turn results in compromised centromere integrity and abnormal chromosome separation and hinders cancer cell proliferation and tumor growth. Our findings unveil an m<sup>6</sup>A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potential targets for cancer therapy.</p>\",\"PeriodicalId\":9656,\"journal\":{\"name\":\"Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":45.5000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cell.2024.08.040\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2024.08.040","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells
m6A modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of m6A modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an m6A reader of cenRNA. CENPA is localized at centromeres and is essential in preserving centromere integrity and function during mitosis. The m6A-modified cenRNA stabilizes centromeric localization of CENPA in cancer cells during the S phase of the cell cycle. Mutations of CENPA at the Leu61 and the Arg63 or removal of cenRNA m6A modification lead to loss of centromere-bound CENPA during S phase. This in turn results in compromised centromere integrity and abnormal chromosome separation and hinders cancer cell proliferation and tumor growth. Our findings unveil an m6A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potential targets for cancer therapy.
期刊介绍:
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.