Modulated termination of non-coding transcription partakes in the regulation of gene expression

Abstract

Pervasive transcription is a universal phenomenon leading to the production of a plethora of non-coding RNAs. If left uncontrolled, pervasive transcription can be harmful for genome expression and stability. However, non-coding transcription can also play important regulatory roles, for instance by promoting the repression of specific genes by a mechanism of transcriptional interference. The efficiency of transcription termination can strongly influence the regulatory capacity of non-coding transcription events, yet very little is known about the mechanisms modulating the termination of non-coding transcription in response to environmental cues. Here, we address this question by investigating the mechanisms that regulate the activity of the main actor in termination of non-coding transcription in budding yeast, the helicase Sen1. We identify a phosphorylation at a conserved threonine of the catalytic domain of Sen1 and we provide evidence that phosphorylation at this site reduces the efficiency of Sen1-mediated termination. Interestingly, we find that this phosphorylation impairs termination at an unannotated non-coding gene, thus repressing the expression of a downstream gene encoding the master regulator of Zn homeostasis, Zap1. Consequently, many additional genes exhibit an expression pattern mimicking conditions of Zn excess, where ZAP1 is naturally repressed. Our findings provide a novel paradigm of gene regulatory mechanism relying on the direct modulation of non-coding transcription termination.