The INO80 ATP-dependent chromatin remodelling complex alleviates stalled Polymerase II to promote non-coding RNA transcription termination.

Abstract

Co-transcriptional RNA quality control is essential for gene expression. However, its regulation remains poorly understood. Here, we report that the evolutionarily conserved ATP-dependent chromatin remodelling INO80 complex promotes transcription termination by the non-coding RNA quality control pathway in S. cerevisiae. Loss of INO80 leads to accumulation of stalled RNA Polymerase II preferentially at promoter-proximal pausing sites, compromising Pol II processivity and hindering transcription elongation. We reveal that binding of RNA surveillance and non-coding transcription termination factors to promoter-proximal mRNA regions is associated with increased promoter-proximal pausing. INO80 counteracts promoter-proximal stalling of genes attenuated by the Nrd1-Nab3-Sen1 (NNS) non-coding transcription termination complex, promoting their expression. We show that INO80 interacts with Nrd1 and the Nab2 RNA surveillance factor in vivo. Absence of INO80 leads to defective transcription termination by the Nrd1-Nab3-Sen1 (NNS) complex. We demonstrate that INO80 facilitates the recruitment of Nab2 at non-coding transcription termination sites and its association with promoter-proximally terminated mRNA transcripts. Finally, we provide evidence that INO80 promotes the release of stalled RNA Polymerase II from a non-coding transcription termination site. Collectively, our work suggests that the INO80 complex regulates transcription by removal of stalled Polymerase, implicating a chromatin-based mechanism for non-coding and premature transcription termination in gene expression.