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m 5 C methylated lncRncr3-MeCP2 interaction restricts miR124a-initiated neurogenesis.
- Source :
-
Nature communications [Nat Commun] 2024 Jun 15; Vol. 15 (1), pp. 5136. Date of Electronic Publication: 2024 Jun 15. - Publication Year :
- 2024
-
Abstract
- Coordination of neuronal differentiation with expansion of the neuroepithelial/neural progenitor cell (NEPC/NPC) pool is essential in early brain development. Our in vitro and in vivo studies identify independent and opposing roles for two neural-specific and differentially expressed non-coding RNAs derived from the same locus: the evolutionarily conserved lncRNA Rncr3 and the embedded microRNA miR124a-1. Rncr3 regulates NEPC/NPC proliferation and controls the biogenesis of miR124a, which determines neuronal differentiation. Rncr3 conserved exons 2/3 are cytosine methylated and bound by methyl-CpG binding protein MeCP2, which restricts expression of miR124a embedded in exon 4 to prevent premature neuronal differentiation, and to orchestrate proper brain growth. MeCP2 directly binds cytosine-methylated Rncr3 through previously unrecognized lysine residues and suppresses miR124a processing by recruiting PTBP1 to block access of DROSHA-DGCR8. Thus, miRNA processing is controlled by lncRNA m <superscript>5</superscript> C methylation along with the defined m <superscript>5</superscript> C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Brain metabolism
Brain embryology
Humans
Cell Differentiation
DNA Methylation
Polypyrimidine Tract-Binding Protein metabolism
Polypyrimidine Tract-Binding Protein genetics
Cell Proliferation
Mice, Inbred C57BL
5-Methylcytosine metabolism
5-Methylcytosine analogs & derivatives
Male
Exons genetics
Neurons metabolism
Ribonuclease III
MicroRNAs metabolism
MicroRNAs genetics
Methyl-CpG-Binding Protein 2 metabolism
Methyl-CpG-Binding Protein 2 genetics
Neurogenesis genetics
RNA, Long Noncoding metabolism
RNA, Long Noncoding genetics
Neural Stem Cells metabolism
Neural Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38879605
- Full Text :
- https://doi.org/10.1038/s41467-024-49368-w