| First Author | Zhang J | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 5136 |
| PubMed ID | 38879605 | Mgi Jnum | J:349888 |
| Mgi Id | MGI:7659988 | Doi | 10.1038/s41467-024-49368-w |
| Citation | Zhang J, et al. (2024) m(5)C methylated lncRncr3-MeCP2 interaction restricts miR124a-initiated neurogenesis. Nat Commun 15(1):5136 |
| abstractText | 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(5)C methylation along with the defined m(5)C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development. |
