| Literature DB >> 35927451 |
Xueju Wei1,2,3, Yue Huo1,2, Jingnan Pi1,2, Yufeng Gao1,2, Shuan Rao4, Manman He1,2, Qinglv Wei1,2, Peng Song5, Yiying Chen1,2, Dongxu Lu1,2, Wei Song1,2, Junbo Liang1,2, Lingjie Xu6, Haixia Wang7, Guolin Hong3, Yuehong Guo1,2, Yanmin Si1,2, Jiayue Xu1,2, Xiaoshuang Wang1,2, Yanni Ma1,2, Shuyang Yu8, Dongling Zou9, Jing Jin10,11, Fang Wang12,13, Jia Yu14,15.
Abstract
METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression. In gastric cancer, METTL3 could not only facilitate cancer progression via m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3. Mechanistically, cytoplasm-anchored METTL3 interacted with PABPC1 to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded to prostate cancer. Therefore, the cytoplasmic METTL3 enhances the translation of epigenetic mRNAs, thus serving as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnosis and predict prognosis for patients with cancer.Entities:
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Year: 2022 PMID： 35927451 DOI： 10.1038/s41556-022-00968-y
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.213