Rtf1-dependent transcriptional pausing regulates cardiogenesis.

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

SUBMITTER: Langenbacher AD 

PROVIDER: S-EPMC12807453 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature