Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma

作者：Yixian Cun, Sanqi An, Hai-Qing Zheng, Jing Lan, Wen-Fang Chen, Wanjun Luo, C. Yao, Xincheng Li, Xiang Huang, Xiang Sun, Ze-Hong Wu, Yameng Hu, Zi-Wen Li, Shuxia Zhang, Ge-Yan Wu, Meisongzhu Yang, Miaoling Tang, Ruyuan Yu, Xinyi Liao, Gui-Cheng Gao, Wei Zhao, Jin-Kai Wang, Jun Li · 发表于：Genomics, Proteomics & Bioinformatics · 年份：2021 · DOI：10.1016/j.gpb.2021.11.001 · 被引用次数：36 · 研究领域：Medicine、Computer Science

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs).