Genome-wide Analysis of RNA Polymerase II Termination at Protein-Coding Genes

• Published in: Molecular cell 2017-04, Vol.66 (1), p.38-49.e6
• Main Authors: Baejen, Carlo, Andreani, Jessica, Torkler, Phillipp, Battaglia, Sofia, Schwalb, Bjoern, Lidschreiber, Michael, Maier, Kerstin C., Boltendahl, Andrea, Rus, Petra, Esslinger, Stephanie, Söding, Johannes, Cramer, Patrick
• Format: Article
• Language: English
• Subjects: Binding Sites; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; DNA, Fungal - genetics; DNA, Fungal - metabolism; Exoribonucleases - genetics; Exoribonucleases - metabolism; Medicin och hälsovetenskap; Models, Genetic; mRNA Cleavage and Polyadenylation Factors - genetics; mRNA Cleavage and Polyadenylation Factors - metabolism; poly-adenylation; pre-mRNA 3′-processing; Protein Binding; RNA 3' End Processing; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; RNA Precursors - biosynthesis; RNA Precursors - genetics; RNA, Fungal - biosynthesis; RNA, Fungal - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Torpedo nuclease; transcription termination; Transcriptional Elongation Factors - genetics; Transcriptional Elongation Factors - metabolism
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2017.02.009

At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3′-processing of the pre-mRNA and transcription termination. Here, we present a genome-wide analysis of the 3′-transition in budding yeast. We find that the 3′-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and requires the “torpedo” exonuclease Rat1 (XRN2 in human). The Rat1-interacting factor Rai1 contributes to RNA degradation downstream of the pA site. Defects in the 3′-transition can result in increased transcription at downstream genes. [Display omitted] •Pcf11 and Ysh1 are globally required for the 3′-transition at protein-coding genes•Spt5 binds pre-mRNA near the pA site and contributes to the 3′-transition•Rat1 is globally required for Pol II release from DNA in a narrow termination window RNA polymerase II undergoes a concerted transition at the 3′ end of protein coding genes. Baejen et al. present a genome-wide analysis of this 3′-transition in budding yeast. They show that this transition requires the Spt5 elongation factor and demonstrate that polymerase II release from DNA requires the Rat1 exonuclease.