Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage
- Irina Poverennaya
- Aliia Murtazina
- Lei Li
- Lorena Maili
- Lukas Sourada
- Luis Fernando Montano-Gutierrez
- Rozalina Galimullina
- Tobias Steinschaden
- Marketa Kaiser
- Tomas Zikmund
- Adna Goralija
- Teng Gao
- Aurore Attina
- Ornella Clara
- Christoph Bartenhagen
- Alek Erickson
- Yaakov Gershtein
- Shiyuan Chen
- Kristyna Polaskova
- Jaroslav Sterba
- Bettina Semasch
- Emma R. Anderson
- Varsha Prakash
- Theresa Vincent
- Maria Arceo
- Per Kogner
- Susanne Schlisio
- Peter V. Kharchenko
- Alexandre David
- Jozef Kaiser
- Matthias Fischer
- Jan Skoda
- Paul A. Trainor
- Andrei S. Chagin
- Igor Adameyko
2026-03-09
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 m¹acp³ψ 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 m¹acp³ψ 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.