Translation sustains productive Pol II elongation through maintenance of nuclear RNA surveillance

Abstract

Although transcription and translation are spatially separated in eukaryotic cells, gene expression requires coordination between the nucleus and cytoplasm. Whether translation rapidly influences nuclear transcription remains unclear. Here we show that ongoing translation sustains productive RNA polymerase II (Pol II) elongation in mouse embryonic stem cells. Translation inhibition reduces nascent transcription within 15 minutes, impairs Pol II pause release, and preferentially represses long genes before substantial loss of chromatin-associated Pol II. Unexpectedly, despite reduced transcription, nuclear RNA transiently accumulates owing impaired in RNA turnover. Mechanistically, translational arrest redistributes RNA-processing and RNA-surveillance factors from the nucleus to stalled ribosome-associated complexes in the cytoplasm, reducing their nuclear availability. Acute depletion of RNA-surveillance components phenocopies elongation defects caused by translational inhibition, particularly in long genes. Together, our findings identify ongoing translation as a regulator of nuclear RNA surveillance capacity and reveal a feedback mechanism sustaining productive Pol II elongation and nuclear RNA homeostasis.