RNA pol II speed controls the level of read-through mediated transcriptional interference

Abstract Transcriptional interference, which can be mediated by read-through transcription, is recognized as a mechanism negatively controlling gene expression levels. Recent studies highlighted the importance of transcriptional interference mediated by read-through transcription in response to different kinds of stresses and in response to viral infections. In this study we investigated the extent of transcriptional interference mediated by read-through transcription in different human cell lines. Our results, based on the analysis of transcriptomics and genomics data, reveal that transcriptional interference is widespread in the human genome in unperturbed conditions. Furthermore, through the use of RNA pol II mutants with different velocity, we show that transcriptional interference can be controlled by RNA pol II speed. Finally, we observe that read-through transcription invading downstream genes significantly associates with decreased level of translation of downstream genes in tandem gene pairs, therefore probably affecting protein levels. Together these data indicate that transcriptional interference is a mechanism controlling gene expression in unperturbed conditions. In addition, our results uncover the importance of transcription speed in controlling the expression level of downstream genes in tandem gene pairs.