信使核糖核酸
应力颗粒
生物
P-体
翻译效率
蛋白质生物合成
翻译(生物学)
细胞生物学
基因表达
转录组
分子生物学
基因
遗传学
作者
Zhicong Zhao,Ying Qing,Lei Dong,Li Han,Wei Dong,Yangchan Li,Wei Li,Jianhuang Xue,Keren Zhou,Miao Sun,Brandon Tan,Zhenhua Chen,Chao Shen,Lei Gao,Andrew Small,Kitty Wang,Keith Leung,Zheng Zhang,Xi Qin,Xiaolan Deng,Qiang Xia,Rui Su,Jianjun Chen
出处
期刊:Cell
[Elsevier]
日期:2023-07-01
卷期号:186 (15): 3208-3226.e27
被引量:17
标识
DOI:10.1016/j.cell.2023.05.047
摘要
N7-methylguanosine (m7G) modification, routinely occurring at mRNA 5′ cap or within tRNAs/rRNAs, also exists internally in messenger RNAs (mRNAs). Although m7G-cap is essential for pre-mRNA processing and protein synthesis, the exact role of mRNA internal m7G modification remains elusive. Here, we report that mRNA internal m7G is selectively recognized by Quaking proteins (QKIs). By transcriptome-wide profiling/mapping of internal m7G methylome and QKI-binding sites, we identified more than 1,000 high-confidence m7G-modified and QKI-bound mRNA targets with a conserved “GANGAN (N = A/C/U/G)” motif. Strikingly, QKI7 interacts (via C terminus) with the stress granule (SG) core protein G3BP1 and shuttles internal m7G-modified transcripts into SGs to regulate mRNA stability and translation under stress conditions. Specifically, QKI7 attenuates the translation efficiency of essential genes in Hippo signaling pathways to sensitize cancer cells to chemotherapy. Collectively, we characterized QKIs as mRNA internal m7G-binding proteins that modulate target mRNA metabolism and cellular drug resistance.
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