Heat shock-mediated global gene downregulation is achieved by premature transcription termination [4SU_mRNA-seq]

The Heat Shock response (HSR) is a highly conserved transcriptional program induced by the exposure to a variety of environmental stressors. Following an insult, a small subset of genes, known as the Heat Shock genes, are rapidly induced by the Heat Shock Factors (HSFs) to maintain protein homeostasis and ensure cell survival. In parallel, a large portion of the genome becomes repressed. HS associated global gene repression is still largely poorly understood. In this study, we demonstrate that transcription downregulation during Heat shock is mainly achieved by premature transcription termination through the regulation of U1snRNA and the disruption of U1-telescripting. Newly-made mRNAs synthesized during HS were selected by labelling the RNA with 4SU and selecting the polyA(+) fraction of the labelled RNA.