Journal
MOLECULAR CELL
Volume 80, Issue 4, Pages 633-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2020.10.026
Keywords
-
Categories
Funding
- NIH [F32 CA221007, CA247175, HG008935]
Ask authors/readers for more resources
N-6-methyladenosine (m(6)A) is the most abundant mRNA modification and is installed by the METTL3-METTL14-WTAP methyltransferase complex. Although the importance of m(6)A methylation in mRNA metabolism has been well documented recently, regulation of the m(6)A 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 m(6)A methyltransferase complex. Lack of METTL3/WTAP phosphorylation reduces decay of m(6)A-labeled pluripotent factor transcripts and traps mouse embryonic stem cells in the pluripotent state. The same phosphorylation can also be found in ERKactivated human cancer cells and contribute to tumorigenesis. Our study reveals an unrecognized function of ERK in regulating m(6)A methylation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available