Acute stress drives global repression through two independent RNA polymerase II stalling events in Saccharomyces

• Published in: Cell reports (Cambridge) 2021-01, Vol.34 (3), p.108640-108640, Article 108640
• Main Authors: Badjatia, Nitika, Rossi, Matthew J., Bataille, Alain R., Mittal, Chitvan, Lai, William K.M., Pugh, B. Franklin
• Format: Article
• Language: English
• Subjects: DSIF; peroxide stress; Pol II pausing; promoter-proximal pausing; RNA Polymerase II - metabolism; Saccharomyces - genetics; Stress, Physiological - genetics; transcription elongation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108640

In multicellular eukaryotes, RNA polymerase (Pol) II pauses transcription ~30–50 bp after initiation. While the budding yeast Saccharomyces has its transcription mechanisms mostly conserved with other eukaryotes, it appears to lack this fundamental promoter-proximal pausing. However, we now report that nearly all yeast genes, including constitutive and inducible genes, manifest two distinct transcriptional stall sites that are brought on by acute environmental signaling (e.g., peroxide stress). Pol II first stalls at the pre-initiation stage before promoter clearance, but after DNA melting and factor acquisition, and may involve inhibited dephosphorylation. The second stall occurs at the +2 nucleosome. It acquires most, but not all, elongation factor interactions. Its regulation may include Bur1/Spt4/5. Our results suggest that a double Pol II stall is a mechanism to downregulate essentially all genes in concert. [Display omitted] •Acute stress causes promoter-proximal Pol II stalling at most yeast genes•Pol II maintains an open bubble but stops transcribing•Stalling occurs at two locations: at promoters and at +2 nucleosomes•Stalling precedes stress-induced gene reprogramming Unlike metazoans, transcription in budding yeast proceeds rapidly from start to end. However, Badjatia et al. now show that acute stress causes Pol II to stall at two primary locations at the 5′ ends of most yeast genes. Stalling may facilitate rapid gene silencing, which promotes stress-induced gene-specific reprogramming.