PUBLICATION
RNA Polymerase III subunit Polr3a is required for craniofacial cartilage and bone development in zebrafish
- Authors
- Lubash, B.T., Gutierrez, R., Hansen, N.A., Fink, K., Hopkins, C.A., Sands, L.B., Nelson, J.C., Watt, K.E.N.
- ID
- ZDB-PUB-260609-9
- Date
- 2026
- Source
- PLoS Genetics 22: e1012164e1012164 (Journal)
- Registered Authors
- Watt, Kristin
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 42258504 Full text @ PLoS Genet.
Citation
Lubash, B.T., Gutierrez, R., Hansen, N.A., Fink, K., Hopkins, C.A., Sands, L.B., Nelson, J.C., Watt, K.E.N. (2026) RNA Polymerase III subunit Polr3a is required for craniofacial cartilage and bone development in zebrafish. PLoS Genetics. 22:e1012164e1012164.
Abstract
Transcription by RNA Polymerase III (Pol III) is essential for ribosome biogenesis and translation in all cells, but pathogenic variants in genes encoding subunits of Pol III lead to tissue-specific phenotypes including craniofacial differences. To understand the function of Pol III in craniofacial development, we examined polr3a mutant zebrafish. These mutants display hypoplasia of the neural crest cell-derived craniofacial cartilage and bone but, surprisingly, no significant changes were observed in neural crest cell proliferation or survival during embryogenesis. At larval stages, increased cell death was observed throughout the head, including in the craniofacial cartilage. These changes coincide with reduced transcription of transfer RNAs and reduced ribosome biogenesis in polr3a mutant zebrafish. To determine tissue-specific transcriptional changes, we performed single-cell RNA-sequencing. Analysis revealed both global and cartilage-specific changes, including upregulation of tp53. However, Tp53 inhibition alone was not sufficient to rescue craniofacial cartilage and bone, indicating that additional factors are important to support cartilage and bone growth in polr3a mutants. Altogether, our study provides new mechanistic insights into the functions of Pol III in craniofacial development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping