Transcription and chromatin-based surveillance mechanism controls suppression of cryptic antisense transcription

• Published in: Cell reports (Cambridge) 2021-09, Vol.36 (10), p.109671-109671, Article 109671
• Main Authors: Heo, Dong-Hyuk, Kuś, Krzysztof, Grzechnik, Pawel, Tan-Wong, Sue Mei, Birot, Adrien, Kecman, Tea, Nielsen, Soren, Zenkin, Nikolay, Vasiljeva, Lidia
• Format: Article
• Language: English
• Subjects: Chromatin - metabolism; convergent genes; cryptic antisense transcription; Gene Expression Regulation, Fungal - physiology; histone deacetylase; Histone Deacetylases - metabolism; Histones - metabolism; Hos2/Set3 complex; RNA Polymerase II - metabolism; RNA polymerase II phosphorylation; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Ssu72 phosphatase; transcription termination
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109671

Phosphorylation of the RNA polymerase II C-terminal domain Y1S2P3T4S5P6S7 consensus sequence coordinates key events during transcription, and its deregulation leads to defects in transcription and RNA processing. Here, we report that the histone deacetylase activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of antisense transcription when RNA polymerase II phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, although single Hos2 and Set3 mutants have little effect, loss of Hos2 or Set3 combined with ssu72Δ results in a synergistic increase in antisense transcription globally and correlates with elevated sensitivity to genotoxic agents. We demonstrate a key role for the Ssu72/Hos2/Set3 mechanism in the suppression of cryptic antisense transcription at the 3′ end of convergent genes that are most susceptible to these defects, ensuring the fidelity of gene expression within dense genomes of simple eukaryotes. [Display omitted] •Conserved phosphatase Ssu72 controls RNA polymerase II phosphorylation•Ssu72 is required for transcription termination at convergent genes•Antisense transcription is globally increased in the absence of Ssu72•HDAC Hos2 acts in the absence of Ssu72 to minimize antisense transcription Unwanted antisense transcription might be detrimental for the cell. Heo et al. demonstrate that conserved RNA polymerase II phosphatase Ssu72 and histone deacetylase Hos2 collaborate to keep under control the cryptic antisense transcription that arises from the fission yeast genome.