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Stabilization of ERK-Phosphorylated METTL3 by USP5 Increases m6A Methylation.
Sun, Hui-Lung; Zhu, Allen C; Gao, Yawei; Terajima, Hideki; Fei, Qili; Liu, Shun; Zhang, Linda; Zhang, Zijie; Harada, Bryan T; He, Yu-Ying; Bissonnette, Marc B; Hung, Mien-Chie; He, Chuan.
  • Sun HL; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Zhu AC; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, The University of Chicago, Chicago, IL 60637, USA.
  • Gao Y; Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • Terajima H; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Fei Q; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Liu S; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Zhang L; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Zhang Z; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • Harada BT; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
  • He YY; Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL 60637, USA.
  • Bissonnette MB; Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
  • Hung MC; China Medical University, Taichung 404, Taiwan.
  • He C; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA. Electr
Mol Cell ; 80(4): 633-647.e7, 2020 11 19.
Article en En | MEDLINE | ID: mdl-33217317
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Endopeptidasas / Adenina / Quinasas MAP Reguladas por Señal Extracelular / Carcinogénesis / Melanoma / Metiltransferasas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
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PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Endopeptidasas / Adenina / Quinasas MAP Reguladas por Señal Extracelular / Carcinogénesis / Melanoma / Metiltransferasas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2020 Tipo del documento: Article