m6A modification regulates PLK1 expression and mitosis.
- Author:
Xiaoli CHANG
1
;
Xin YAN
1
;
Zhenyu YANG
2
;
Shuwen CHENG
3
;
Xiaofeng ZHU
4
;
Zhantong TANG
5
;
Wenxia TIAN
1
;
Yujun ZHAO
1
;
Yongbo PAN
5
;
Shan GAO
5
Author Information
- Publication Type:Journal Article
- Keywords: cell cycle; methyltransferase-like 3 (METTL3); mitosis; polo-like kinase 1 (PLK1)
- MeSH: Humans; Polo-Like Kinase 1; Cell Cycle Proteins/metabolism*; Proto-Oncogene Proteins/metabolism*; Protein Serine-Threonine Kinases/metabolism*; Mitosis/physiology*; HeLa Cells; Adenosine/genetics*; Methyltransferases/metabolism*; RNA, Messenger/metabolism*; RNA-Binding Proteins/metabolism*
- From: Chinese Journal of Biotechnology 2025;41(4):1559-1572
- CountryChina
- Language:Chinese
- Abstract: N6-methyladenosine (m6A) modification plays a critical role in cell cycle regulation, while the mechanism of m6A in regulating mitosis remains underexplored. Here, we found that the total m6A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m6A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m6A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m6A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m6A modification inhibits PLK1 translation via YTH N6-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m6A in regulating mitosis and the potential of m6A as a therapeutic target in proliferative diseases such as cancer.
