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  3. Nuclear m6A modification regulates satellite transcription and chromosome segregation

Nuclear m6A modification regulates satellite transcription and chromosome segregation

  • Nat Chem Biol. 2025 May 22. doi: 10.1038/s41589-025-01900-9.
Chenyang Huang # 1,  Xiao Shu # 1 2,  Siting Zhou # 3 4,  Yujie Mi 1,  Hanxiao Bian 5,  Ting Li 1,  Tengwei Li 1,  Xiner Ying 1,  Chongguang Cheng 1,  Donghong Liu 1,  Minsong Gao 1,  Yongjian Wen 1,  Quan Ma 6,  Fengqin Wang 7,  Jie Cao 8 9,  Jinkai Wang 10 11,  Jianzhao Liu 12 13 14 15
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.
  • 2 College of Materials and Chemistry & Chemical Engineering, Chengdu University of Technology, Chengdu, China.
  • 3 Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 4 Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.
  • 5 Laboratory of Fruit Quality Biology, Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou, China.
  • 6 College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China.
  • 7 College of Animal Sciences, Key Laboratory of Animal Nutrition & Feed Sciences, Ministry of Agriculture, Zhejiang University, Hangzhou, China.
  • 8 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China. cao_jie@zju.edu.cn.
  • 9 Life Sciences Institute, Zhejiang University, Hangzhou, China. cao_jie@zju.edu.cn.
  • 10 Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. wangjk@mail.sysu.edu.cn.
  • 11 Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, China. wangjk@mail.sysu.edu.cn.
  • 12 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China. liujz@zju.edu.cn.
  • 13 Life Sciences Institute, Zhejiang University, Hangzhou, China. liujz@zju.edu.cn.
  • 14 State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China. liujz@zju.edu.cn.
  • 15 Center for RNA Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China. liujz@zju.edu.cn.
  • # Contributed equally.
PMID: 40404899 DOI: 10.1038/s41589-025-01900-9
Abstract

The precise location and functions of N6-methyladenosine (m6A) modification on mammalian nuclear noncoding RNA remain largely unknown. Here we developed nuclear-m6A-label-seq to directly map human and mouse cell nuclear RNA m6A methylome at single-base resolution. Specifically, m6A modifications have been identified on abundant human γ satellite DNA II (GSATII) RNA transcripts, a type of repeat RNA, transcribed from SST1-TAR1-GSATII satellite arrays in the pericentromeric region of chromosome 9. GSATII RNA m6A positively regulates the transcription of GSATII-located satellite arrays as well as trans-associated peri/centromeric satellites, typically chromosome 3 centromeric higher-order repeat α satellite. Dysregulation of this circuit renders a phenotype of abnormal chromosome segregation. Mechanistic study reveals that YTHDC1 reads GSATII RNA m6A marks and recruits bromodomain protein 4 (BRD4) to promote transcriptions of the associated satellites via an m6A-YTHDC1-BRD4-H3K27ac axis. These results uncover a mechanism governing the transcription of cis- and trans-associated pericentromeric and centromeric satellites via cross-talk between epitranscriptomic and epigenomic marks.

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