Informace o publikaci
Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage
| Autoři | |
|---|---|
| Rok publikování | 2026 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Nature communications |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.nature.com/articles/s41467-026-70375-6 |
| Doi | https://doi.org/10.1038/s41467-026-70375-6 |
| Klíčová slova | Neural crest; tumorigenesis; neuroblastoma; sympathoadrenal development; molecular targets |
| Přiložené soubory | |
| Popis | Neural crest cells contribute to craniofacial formation by differentiating into skeletogenic mesenchyme and neuro-glial lineages. Using Smart-seq2 single-cell transcriptomics, we show that mesenchymal fate commitment correlates specifically with the expression of rRNA-modifying and ribosome assembly factors, rather than structural ribosomal proteins. Notably, EMG1 and NHP2 introduce key post-transcriptional modifications into 18S rRNA, including m & sup1;acp & sup3;psi at U1248, which requires TSR3 for final maturation. Disrupting NHP2 or TSR3 in vitro and in vivo perturbs cranial neural crest differentiation; post-migratory temporal knockout of Polr1a or Polr1c also causes craniofacial malformations. These findings align with cell type-specific m & sup1;acp & sup3;psi levels during neural crest differentiation. Given the neural crest contribution to neuroblastoma, we analyze patient data to find that elevated ribosomal control and rRNA-modifying proteins predict poorer outcomes. Complementary experiments in neuroblastoma cell lines reveal functional roles for TSR3 and WDR74 in mesenchymal-like tumor states. Together, our results link rRNA modifications and ribosome assembly to fate decisions, suggesting ribosomal heterogeneity shapes both normal development and tumor progression. |
| Související projekty: |