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  • Stabilization of ERK-Phosphorylated METTL3 by USP5 Increases m6A Methylation.

Stabilization of ERK-Phosphorylated METTL3 by USP5 Increases m6A Methylation.

Molecular cell (2020-11-21)
Hui-Lung Sun, Allen C Zhu, Yawei Gao, Hideki Terajima, Qili Fei, Shun Liu, Linda Zhang, Zijie Zhang, Bryan T Harada, Yu-Ying He, Marc B Bissonnette, Mien-Chie Hung, Chuan He, Hui-Lung Sun, Allen C Zhu, Yawei Gao, Hideki Terajima, Qili Fei, Shun Liu, Linda Zhang, Zijie Zhang, Bryan T Harada, Yu-Ying He, Marc B Bissonnette, Mien-Chie Hung, Chuan He
PMID33217317
ABSTRACT

N6-methyladenosine (m6A) is the most abundant mRNA modification and is installed by the METTL3-METTL14-WTAP methyltransferase complex. Although the importance of m6A methylation in mRNA metabolism has been well documented recently, regulation of the m6A machinery remains obscure. Through a genome-wide CRISPR screen, we identify the ERK pathway and USP5 as positive regulators of the m6A deposition. We find that ERK phosphorylates METTL3 at S43/S50/S525 and WTAP at S306/S341, followed by deubiquitination by USP5, resulting in stabilization of the m6A methyltransferase complex. Lack of METTL3/WTAP phosphorylation reduces decay of m6A-labeled pluripotent factor transcripts and traps mouse embryonic stem cells in the pluripotent state. The same phosphorylation can also be found in ERK-activated human cancer cells and contribute to tumorigenesis. Our study reveals an unrecognized function of ERK in regulating m6A methylation.

MATERIALS
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Product Description
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Nuclease P1 from Penicillium citrinum, lyophilized powder, ≥200 units/mg protein (E1%/280, 3′-5′-Phosphodiesterase)
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