Chromatin-associated α-satellite RNA maintains chromosome stability by reestablishing SAF-A in the mitotic cell cycle

  • Nucleic Acids Res. 2025 Apr 10;53(7):gkaf294. doi: 10.1093/nar/gkaf294.
Bingbing Ren  1  2 ,  Yinchun Zhong  3 ,  Yan Yang  3 ,  Shuhui Chang  4 ,  Yalun Li  1 ,  Mengzhen You  1 ,  Ge Shan  1  3 ,  Xueren Wang  5  6 ,  Enguo Chen  1
Affiliations
  • 1. Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
  • 2. Central Lab of Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, China.
  • 3. Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • 4. Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
  • 5. Department of Anesthesiology, Shanxi Bethune Hospital, Taiyuan 030032, China.
  • 6. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
PMID: 40219970 DOI: 10.1093/nar/gkaf294
Abstract

α-Satellite is the largest class of tandem repeats and is located on all human chromosome centromeres. Non-coding α-satellite RNAs have been observed in various cell types and are known to play crucial roles in maintaining genome stability. In this study, we demonstrated that α-satellite RNAs are dynamically expressed, heterogeneous transcripts that are regulated by Aurora kinases and closely associated with centromere chromatin throughout the mitotic cell cycle. We identified scaffold attachment factor A (SAF-A) as a previously uncharacterized α-satellite RNA binding protein. Depletion of either α-satellite RNA or SAF-A resulted in chromosome missegregation, revealing that their concerted action is essential for preserving genome integrity during the mitotic cell cycle. Our result demonstrated that SAF-A is excluded from the chromatin genome-wide during Mitosis, and α-satellite RNAs are required for the recruitment of SAF-A upon mitotic exit. Both α-satellite RNAs and SAF-A are essential in safeguarding the human genome against chromosomal instability during Mitosis. Moreover, α-satellite RNAs and SAF-A aid in the reassembly of the nuclear lamina. Our results provide novel insights into the features, regulations, and functional roles of α-satellite RNAs and propose a model for the dismantling and reformation of the SAF-A nuclear scaffold during Mitosis.

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