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METTL3/METTL14 maintain human nucleoli integrity by mediating SUV39H1/H2 degradation.
- Source :
-
Nature communications [Nat Commun] 2024 Aug 21; Vol. 15 (1), pp. 7186. Date of Electronic Publication: 2024 Aug 21. - Publication Year :
- 2024
-
Abstract
- Nucleoli are fundamentally essential sites for ribosome biogenesis in cells and formed by liquid-liquid phase separation (LLPS) for a multilayer condensate structure. How the nucleoli integrity is maintained remains poorly understood. Here, we reveal that METTL3/METTL14, the typical methyltransferase complex catalyzing N6-methyladnosine (m <superscript>6</superscript> A) on mRNAs maintain nucleoli integrity in human embryonic stem cells (hESCs). METTL3/METTL14 deficiency impairs nucleoli and leads to the complete loss of self-renewal in hESCs. We further show that SUV39H1/H2 protein, the methyltransferases catalyzing H3K9me3 were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. Together, these findings uncover a previously unknown role of METTL3/METTL14 to maintain nucleoli integrity by facilitating SUV39H1/H2 degradation in human cells.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Histones metabolism
Ubiquitination
Human Embryonic Stem Cells metabolism
Proteolysis
HEK293 Cells
Ubiquitin-Protein Ligases metabolism
Ubiquitin-Protein Ligases genetics
Histone-Lysine N-Methyltransferase
Methyltransferases metabolism
Methyltransferases genetics
Cell Nucleolus metabolism
Repressor Proteins metabolism
Repressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39169036
- Full Text :
- https://doi.org/10.1038/s41467-024-51742-7