m<sup>5</sup>C methylated lncRncr3-MeCP2 interaction restricts miR124a-initiated neurogenesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38879605.
- Also identified by DOI 10.1038/s41467-024-49368-w and PMC identifier 11180186.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>5</sup>C methylation along with the defined m<sup>5</sup>C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.
Medical subject headings
- MicroRNAs
- Methyl-CpG-Binding Protein 2
- Neurogenesis
- RNA, Long Noncoding
- Neural Stem Cells