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| Status |
Public on May 16, 2022 |
| Title |
METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumorigenesis (meRIP, RIP and polysome-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Methyltransferase-like 3 (METTL3) is the best known m6A methyltransferase of the N6-adenosine-methyltransferase complex that functions in the reversible epi-transcriptome modulation of m6A modification. Besides acting as a m6A methyltransferase, METTL3 also regulates mRNA translation as well as other biological processes either through m6A “reader”-mediated downstream effect or directly binding to m6A sites, but the underlying mechanism and biological significance of these cytoplasmic events remain undefined. Here, we demonstrated that METTL3 inhibition significantly delayed gastric tumorigenesis in patient-derived xenograft model. Intriguingly, global METTL3-binding profiling revealed METTL3 occupied numerous oncogenic mRNAs without m6A signals, indicating a novel mechanism independent of m6A machinery. Furthermore, METTL3 was observed to translocate from nucleus to cytoplasm during gastric carcinogenesis, and its cytoplasm-to-nucleus ratio was correlated with cancer progression. In addition, the nuclear retention of METTL3 nearly abolished its tumor-promoting activity. Mechanistically, METTL3 interacted with PABPC1 to promote RNA looping, thus facilitating the translation of multiple oncogenic mRNAs. Taken together, our findings indicate an unexpected role of METTL3 as an important translational regulator independent of either m6A-“writer” or -“reader” activities and suggest METTL3 as a therapeutic target in gastric cancer.
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| Overall design |
Examination the cytoplasmic function of METTL3 in human gastric cancer
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| Contributor(s) |
Wei X, Pi J, Huo Y, Gao Y, Wei Q, Wang F, Jia Y |
| Citation missing |
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| |
| Submission date |
Dec 16, 2020 |
| Last update date |
May 18, 2022 |
| Contact name |
Yufeng Gao |
| E-mail(s) |
gaoyufeng@ibms.pumc.edu.cn
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| Organization name |
Chinese Academy of Medical Sciences & Peking Union Medical College
|
| Department |
State Key Laboratory of Medical Molecular Biology
|
| Street address |
Dong Dan San Tiao 5
|
| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100005 |
| Country |
China |
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| Platforms (1) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA685739 |
| SRA |
SRP298113 |
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