PUBLICATION
Rtf1-dependent transcriptional pausing regulates cardiogenesis
- Authors
- Langenbacher, A.D., Lu, F., Tsang, L., Huang, Z.Y.S., Keer, B., Tian, Z., Eide, A., Pellegrini, M., Nakano, H., Nakano, A., Chen, J.N.
- ID
- ZDB-PUB-260116-8
- Date
- 2026
- Source
- eLIFE 13: (Journal)
- Registered Authors
- Chen, Jau-Nian, Langenbacher, Adam
- Keywords
- PAF1 complex, Rtf1, cardiogenesis, developmental biology, lateral plate mesoderm, mouse, promoter-proximal pausing, transcription regulation, zebrafish
- MeSH Terms
-
- Animals
- Cell Differentiation
- Chromosomal Proteins, Non-Histone
- Cyclin-Dependent Kinase 9/metabolism
- Gene Expression Regulation, Developmental*
- Heart*/embryology
- Mice
- Myocytes, Cardiac/metabolism
- RNA Polymerase II/metabolism
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Transcription, Genetic*
- Transcriptional Elongation Factors/metabolism
- Zebrafish/embryology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41537425 Full text @ Elife
Citation
Langenbacher, A.D., Lu, F., Tsang, L., Huang, Z.Y.S., Keer, B., Tian, Z., Eide, A., Pellegrini, M., Nakano, H., Nakano, A., Chen, J.N. (2026) Rtf1-dependent transcriptional pausing regulates cardiogenesis. eLIFE. 13:.
Abstract
Transcriptional pause-release critically regulates cellular RNA biogenesis, yet how dysregulation of this process impacts embryonic development is not fully understood. Rtf1 is a multifunctional transcription regulatory protein involved in modulating promoter-proximal pausing of RNA Polymerase II (RNA Pol II). Using zebrafish and mouse as model systems, we show that Rtf1 activity is essential for the differentiation of the myocardial lineage from mesoderm. Ablation of rtf1 impairs the formation of nkx2.5+/tbx5a+ cardiac progenitor cells, resulting in the development of embryos without cardiomyocytes. Structure-function analysis demonstrates that Rtf1's cardiogenic activity requires its Plus3 domain, which confers interaction with the pausing/elongation factor Spt5. In Rtf1-deficient embryos, the occupancy of RNA Pol II at transcription start sites was reduced relative to downstream occupancy, suggesting a reduction in transcriptional pausing. Intriguingly, attenuating pause release by pharmacological inhibition or morpholino targeting of CDK9 improved RNA Pol II occupancy at the transcription start sites of key cardiac genes and restored cardiomyocytes in Rtf1-deficient embryos. Thus, our findings demonstrate the crucial role that Rtf1-mediated transcriptional pausing plays in controlling the precise spatiotemporal transcription programs that govern early heart development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping