ARS2 is a general suppressor of pervasive transcription. Issue 17 (29th September 2017)

• Record Type: Journal Article
• Authors: Iasillo, Claudia; Schmid, Manfred; Yahia, Yousra; Maqbool, Muhammad A.; Descostes, Nicolas; Karadoulama, Evdoxia; Bertrand, Edouard; Andrau, Jean-Christophe; Jensen, Torben Heick
• Is Part Of: Nucleic acids research. Volume 45:Issue 17(2017)
• Page Start: 10229
• Page End: 10241
• Publication Date: 2017-09-29
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx647
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Termination of transcription is important for establishing gene punctuation marks. It is also critical for suppressing many of the pervasive transcription events occurring throughout eukaryotic genomes and coupling their RNA products to efficient decay. In human cells, the ARS2 protein has been implicated in such function as its depletion causes transcriptional read-through of selected gene terminators and because it physically interacts with the ribonucleolytic nuclear RNA exosome. Here, we study the role of ARS2 on transcription and RNA metabolism genome wide. We show that ARS2 depletion negatively impacts levels of promoter-proximal RNA polymerase II at protein-coding (pc) genes. Moreover, our results reveal a general role of ARS2 in transcription termination-coupled RNA turnover at short transcription units like snRNA-, replication-dependent histone-, promoter upstream transcript- and enhancer RNA-loci. Depletion of the ARS2 interaction partner ZC3H18 mimics the ARS2 depletion, although to a milder extent, whereas depletion of the exosome core subunit RRP40 only impacts RNA abundance post-transcriptionally. Interestingly, ARS2 is also involved in transcription termination events within first introns of pc genes. Our work therefore establishes ARS2 as a general suppressor of pervasive transcription with the potential to regulate pc gene expression.