The Role of Rat1 in Coupling MRNA 3'-end Processing to Transcription Termination: Implications for a Unified Allosteric-torpedo Model

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2006 Apr 7

PMID 16598041

Citations 104

Authors

Weifei Luo

Arlen W Johnson

David L Bentley

Affiliations

Soon will be listed here.

Abstract

The torpedo model of transcription termination by RNA polymerase II proposes that a 5'-3' RNA exonuclease enters at the poly(A) cleavage site, degrades the nascent RNA, and eventually displaces polymerase from the DNA. Cotranscriptional degradation of nascent RNA has not been directly demonstrated, however. Here we report that two exonucleases, Rat1 and Xrn1, both contribute to cotranscriptional degradation of nascent RNA, but this degradation is not sufficient to cause polymerase release. Unexpectedly, Rat1 functions in both 3'-end processing and termination by enhancing recruitment of 3'-end processing factors, including Pcf11 and Rna15. In addition, the cleavage factor Pcf11 reciprocally aids in recruitment of Rat1 to the elongation complex. Our results suggest a unified allosteric/torpedo model in which Rat1 is not a dedicated termination factor, but is an integrated component of the cleavage/polyadenylation apparatus.

Citing Articles

Defining gene ends: RNA polymerase II CTD threonine 4 phosphorylation marks transcription termination regions genome-wide.

Kopczynska M, Saha U, Romanenko A, Nojima T, Gdula M, Kamieniarz-Gdula K Nucleic Acids Res. 2024; 53(2.

PMID: 39718990 PMC: 11754735. DOI: 10.1093/nar/gkae1240.

Structural basis of eukaryotic transcription termination by the Rat1 exonuclease complex.

Yanagisawa T, Murayama Y, Ehara H, Goto M, Aoki M, Sekine S Nat Commun. 2024; 15(1):7854.

PMID: 39245712 PMC: 11381523. DOI: 10.1038/s41467-024-52157-0.

Arabidopsis and maize terminator strength is determined by GC content, polyadenylation motifs and cleavage probability.

Gorjifard S, Jores T, Tonnies J, Mueth N, Bubb K, Wrightsman T Nat Commun. 2024; 15(1):5868.

PMID: 38997252 PMC: 11245536. DOI: 10.1038/s41467-024-50174-7.

Chromatin regulates alternative polyadenylation via the RNA polymerase II elongation rate.

Geisberg J, Moqtaderi Z, Struhl K Proc Natl Acad Sci U S A. 2024; 121(21):e2405827121.

PMID: 38748572 PMC: 11127049. DOI: 10.1073/pnas.2405827121.

Structural basis of exoribonuclease-mediated mRNA transcription termination.

Zeng Y, Zhang H, Wu X, Zhang Y Nature. 2024; 628(8009):887-893.

PMID: 38538796 DOI: 10.1038/s41586-024-07240-3.

References

Kireeva M, Komissarova N, Waugh D, Kashlev M . The 8-nucleotide-long RNA:DNA hybrid is a primary stability determinant of the RNA polymerase II elongation complex. J Biol Chem. 2000; 275(9):6530-6. DOI: 10.1074/jbc.275.9.6530. View

Stevens A, Poole T . 5'-exonuclease-2 of Saccharomyces cerevisiae. Purification and features of ribonuclease activity with comparison to 5'-exonuclease-1. J Biol Chem. 1995; 270(27):16063-9. DOI: 10.1074/jbc.270.27.16063. View

Schroeder S, Schwer B, Shuman S, Bentley D . Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev. 2000; 14(19):2435-40. PMC: 316982. DOI: 10.1101/gad.836300. View

Bousquet-Antonelli C, Presutti C, Tollervey D . Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell. 2000; 102(6):765-75. DOI: 10.1016/s0092-8674(00)00065-9. View

He F, Jacobson A . Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs. Mol Cell Biol. 2001; 21(5):1515-30. PMC: 86698. DOI: 10.1128/MCB.21.5.1515-1530.2001. View

Gross S, Moore C . Five subunits are required for reconstitution of the cleavage and polyadenylation activities of Saccharomyces cerevisiae cleavage factor I. Proc Natl Acad Sci U S A. 2001; 98(11):6080-5. PMC: 33425. DOI: 10.1073/pnas.101046598. View

Calvo O, Manley J . Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination. Mol Cell. 2001; 7(5):1013-23. DOI: 10.1016/s1097-2765(01)00236-2. View

Steinmetz E, Conrad N, Brow D, Corden J . RNA-binding protein Nrd1 directs poly(A)-independent 3'-end formation of RNA polymerase II transcripts. Nature. 2001; 413(6853):327-31. DOI: 10.1038/35095090. View

Licatalosi D, Geiger G, Minet M, Schroeder S, Cilli K, McNeil J . Functional interaction of yeast pre-mRNA 3' end processing factors with RNA polymerase II. Mol Cell. 2002; 9(5):1101-11. DOI: 10.1016/s1097-2765(02)00518-x. View

10.

Niranjanakumari S, Lasda E, Brazas R, Garcia-Blanco M . Reversible cross-linking combined with immunoprecipitation to study RNA-protein interactions in vivo. Methods. 2002; 26(2):182-90. DOI: 10.1016/S1046-2023(02)00021-X. View

11.

Osheim Y, Sikes M, Beyer A . EM visualization of Pol II genes in Drosophila: most genes terminate without prior 3' end cleavage of nascent transcripts. Chromosoma. 2002; 111(1):1-12. DOI: 10.1007/s00412-002-0183-7. View

12.

Hammell C, Gross S, Zenklusen D, Heath C, Stutz F, Moore C . Coupling of termination, 3' processing, and mRNA export. Mol Cell Biol. 2002; 22(18):6441-57. PMC: 135649. DOI: 10.1128/MCB.22.18.6441-6457.2002. View

13.

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

14.

Orozco I, Kim S, Martinson H . The poly(A) signal, without the assistance of any downstream element, directs RNA polymerase II to pause in vivo and then to release stochastically from the template. J Biol Chem. 2002; 277(45):42899-911. DOI: 10.1074/jbc.M207415200. View

15.

Dichtl B, Blank D, Ohnacker M, Friedlein A, Roeder D, Langen H . A role for SSU72 in balancing RNA polymerase II transcription elongation and termination. Mol Cell. 2002; 10(5):1139-50. DOI: 10.1016/s1097-2765(02)00707-4. View

16.

He X, Khan A, Cheng H, Pappas Jr D, Hampsey M, Moore C . Functional interactions between the transcription and mRNA 3' end processing machineries mediated by Ssu72 and Sub1. Genes Dev. 2003; 17(8):1030-42. PMC: 196040. DOI: 10.1101/gad.1075203. View

17.

Sadowski M, Dichtl B, Hubner W, Keller W . Independent functions of yeast Pcf11p in pre-mRNA 3' end processing and in transcription termination. EMBO J. 2003; 22(9):2167-77. PMC: 156072. DOI: 10.1093/emboj/cdg200. View

18.

Liu Y, Kuersten S, Huang T, Larsen A, Macmorris M, Blumenthal T . An uncapped RNA suggests a model for Caenorhabditis elegans polycistronic pre-mRNA processing. RNA. 2003; 9(6):677-87. PMC: 1370435. DOI: 10.1261/rna.2128903. View

19.

Mandart E, Parker R . Effects of mutations in the Saccharomyces cerevisiae RNA14, RNA15, and PAP1 genes on polyadenylation in vivo. Mol Cell Biol. 1995; 15(12):6979-86. PMC: 230953. DOI: 10.1128/MCB.15.12.6979. View

20.

Gu W, Wind M, Reines D . Increased accommodation of nascent RNA in a product site on RNA polymerase II during arrest. Proc Natl Acad Sci U S A. 1996; 93(14):6935-40. PMC: 38912. DOI: 10.1073/pnas.93.14.6935. View