The Conserved Protein Seb1 Drives Transcription Termination by Binding RNA Polymerase II and Nascent RNA

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Apr 4

PMID 28367989

Citations 34

Authors

Sina Wittmann

Max Renner

Beth R Watts

Oliver Adams

Miles Huseyin

Carlo Baejen

Kamel El Omari

Cornelia Kilchert

Dong-Hyuk Heo

Tea Kecman

Patrick Cramer

Jonathan M Grimes

Lidia Vasiljeva

Affiliations

Soon will be listed here.

Abstract

Termination of RNA polymerase II (Pol II) transcription is an important step in the transcription cycle, which involves the dislodgement of polymerase from DNA, leading to release of a functional transcript. Recent studies have identified the key players required for this process and showed that a common feature of these proteins is a conserved domain that interacts with the phosphorylated C-terminus of Pol II (CTD-interacting domain, CID). However, the mechanism by which transcription termination is achieved is not understood. Using genome-wide methods, here we show that the fission yeast CID-protein Seb1 is essential for termination of protein-coding and non-coding genes through interaction with S2-phosphorylated Pol II and nascent RNA. Furthermore, we present the crystal structures of the Seb1 CTD- and RNA-binding modules. Unexpectedly, the latter reveals an intertwined two-domain arrangement of a canonical RRM and second domain. These results provide important insights into the mechanism underlying eukaryotic transcription termination.

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References

Schulz D, Schwalb B, Kiesel A, Baejen C, Torkler P, Gagneur J . Transcriptome surveillance by selective termination of noncoding RNA synthesis. Cell. 2013; 155(5):1075-87. DOI: 10.1016/j.cell.2013.10.024. View

Logan J, Darnell Jr J, Shenk T . A poly(A) addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene. Proc Natl Acad Sci U S A. 1987; 84(23):8306-10. PMC: 299531. DOI: 10.1073/pnas.84.23.8306. View

Vasiljeva L, Kim M, Mutschler H, Buratowski S, Meinhart A . The Nrd1-Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain. Nat Struct Mol Biol. 2008; 15(8):795-804. PMC: 2597375. DOI: 10.1038/nsmb.1468. View

Core L, Lis J . Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science. 2008; 319(5871):1791-2. PMC: 2833332. DOI: 10.1126/science.1150843. View

Kim M, Vasiljeva L, Rando O, Zhelkovsky A, Moore C, Buratowski S . Distinct pathways for snoRNA and mRNA termination. Mol Cell. 2006; 24(5):723-734. DOI: 10.1016/j.molcel.2006.11.011. View

Tudek A, Porrua O, Kabzinski T, Lidschreiber M, Kubicek K, Fortova A . Molecular basis for coordinating transcription termination with noncoding RNA degradation. Mol Cell. 2014; 55(3):467-81. PMC: 4186968. DOI: 10.1016/j.molcel.2014.05.031. View

Greger I, Proudfoot N . Poly(A) signals control both transcriptional termination and initiation between the tandem GAL10 and GAL7 genes of Saccharomyces cerevisiae. EMBO J. 1998; 17(16):4771-9. PMC: 1170806. DOI: 10.1093/emboj/17.16.4771. View

Bahler J, Wu J, Longtine M, Shah N, McKenzie 3rd A, Steever A . Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast. 1998; 14(10):943-51. DOI: 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO;2-Y. View

Noble C, Hollingworth D, Martin S, Ennis-Adeniran V, Smerdon S, Kelly G . Key features of the interaction between Pcf11 CID and RNA polymerase II CTD. Nat Struct Mol Biol. 2005; 12(2):144-51. DOI: 10.1038/nsmb887. View

10.

Kim H, Erickson B, Luo W, Seward D, Graber J, Pollock D . Gene-specific RNA polymerase II phosphorylation and the CTD code. Nat Struct Mol Biol. 2010; 17(10):1279-86. PMC: 3048030. DOI: 10.1038/nsmb.1913. View

11.

Osheim Y, Proudfoot N, Beyer A . EM visualization of transcription by RNA polymerase II: downstream termination requires a poly(A) signal but not transcript cleavage. Mol Cell. 1999; 3(3):379-87. DOI: 10.1016/s1097-2765(00)80465-7. View

12.

Zhou Y, Zhu J, Schermann G, Ohle C, Bendrin K, Sugioka-Sugiyama R . The fission yeast MTREC complex targets CUTs and unspliced pre-mRNAs to the nuclear exosome. Nat Commun. 2015; 6:7050. PMC: 4455066. DOI: 10.1038/ncomms8050. View

13.

Almada A, Wu X, Kriz A, Burge C, Sharp P . Promoter directionality is controlled by U1 snRNP and polyadenylation signals. Nature. 2013; 499(7458):360-3. PMC: 3720719. DOI: 10.1038/nature12349. View

14.

Schaughency P, Merran J, Corden J . Genome-wide mapping of yeast RNA polymerase II termination. PLoS Genet. 2014; 10(10):e1004632. PMC: 4191890. DOI: 10.1371/journal.pgen.1004632. View

15.

Kobor M, Greenblatt J . Regulation of transcription elongation by phosphorylation. Biochim Biophys Acta. 2002; 1577(2):261-275. DOI: 10.1016/s0167-4781(02)00457-8. View

16.

Xu Z, Wei W, Gagneur J, Perocchi F, Clauder-Munster S, Camblong J . Bidirectional promoters generate pervasive transcription in yeast. Nature. 2009; 457(7232):1033-7. PMC: 2766638. DOI: 10.1038/nature07728. View

17.

Creamer T, Darby M, Jamonnak N, Schaughency P, Hao H, Wheelan S . Transcriptome-wide binding sites for components of the Saccharomyces cerevisiae non-poly(A) termination pathway: Nrd1, Nab3, and Sen1. PLoS Genet. 2011; 7(10):e1002329. PMC: 3197677. DOI: 10.1371/journal.pgen.1002329. View

18.

Zaret K, Sherman F . DNA sequence required for efficient transcription termination in yeast. Cell. 1982; 28(3):563-73. DOI: 10.1016/0092-8674(82)90211-2. View

19.

Kim M, Krogan N, Vasiljeva L, Rando O, Nedea E, Greenblatt J . The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II. Nature. 2004; 432(7016):517-22. DOI: 10.1038/nature03041. View

20.

West S, Gromak N, Proudfoot N . Human 5' --> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. Nature. 2004; 432(7016):522-5. DOI: 10.1038/nature03035. View