IGF2BP3 promotes mRNA degradation through internal m7G modification
Chang Liu, Xiaoyang Dou, Yutao Zhao, Linda Zhang, Lisheng Zhang, Qing Dai, Jun Liu, Tong Wu, Yu Xiao, Chuan He
Abstract
Abstract Recent studies have suggested that mRNA internal m 7 G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m 7 G. Such interactions, especially IGF2BP3 with m 7 G, could promote the degradation of m 7 G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m 7 G modification, while IGF2BP1 prefers m 6 A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53 , is m 7 G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m 7 G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.