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Arginine methylation of METTL14 promotes RNA N6-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- RNA N6-methyladenosine (m6A), the most abundant internal modification of mRNAs, plays key roles in human development and health. Post-translational methylation of proteins is often critical for the dynamic regulation of enzymatic activity. However, the role of methylation of the core methyltransferase METTL3/METTL14 in m6A regulation remains elusive. We find by mass spectrometry that METTL14 arginine 255 (R255) is methylated (R255me). Global mRNA m6A levels are greatly decreased in METTL14 R255K mutant mouse embryonic stem cells (mESCs). We further find that R255me greatly enhances the interaction of METTL3/METTL14 with WTAP and promotes the binding of the complex to substrate RNA. We show that protein arginine N-methyltransferases 1 (PRMT1) interacts with and methylates METTL14 at R255, and consistent with this, loss of PRMT1 reduces mRNA m6A modification globally. Lastly, we find that loss of R255me preferentially affects endoderm differentiation in mESCs. Collectively, our findings show that arginine methylation of METTL14 stabilizes the binding of the m6A methyltransferase complex to its substrate RNA, thereby promoting global m6A modification and mESC endoderm differentiation. This work highlights the crosstalk between protein methylation and RNA methylation in gene expression.<br />The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m6A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m6A methylation activity of the complex.
- Subjects :
- Epigenomics
0301 basic medicine
Protein-Arginine N-Methyltransferases
Adenosine
RNA methylation
Science
General Physics and Astronomy
Stem cells
Arginine
Methylation
Article
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
RNA interference
Gene expression
Protein methylation
Animals
Humans
RNA, Small Interfering
Messenger RNA
Multidisciplinary
Methyltransferase complex
Chemistry
Endoderm
RNA
Cell Differentiation
Mouse Embryonic Stem Cells
Methyltransferases
General Chemistry
RNA modification
Cell biology
HEK293 Cells
030104 developmental biology
Gene Expression Regulation
RNA Interference
Protein Processing, Post-Translational
030217 neurology & neurosurgery
HeLa Cells
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....45dc347211814e44ea7d6795571ad58b