Home LiteratureArticle Details
PMID: 16648491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pause sites promote transcriptional termination of mammalian RNA polymerase II.

Molecular and cellular biology ·Vol. 26 ·No. 10 ·2006-05-00 ·Pages 3986-96

Gromak N, West S, Proudfoot NJ

Abstract

Polymerase II (Pol II) transcriptional termination depends on two independent genetic elements: poly(A) signals and downstream terminator sequences. The latter may either promote cotranscriptional RNA cleavage or pause elongating Pol II. We demonstrate that the previously characterized MAZ4 pause element promotes Pol II termination downstream of a poly(A) signal, dependent on both the proximity of the pause site and poly(A) signal and the strength of the poly(A) signal. The 5'-->3' exonuclease Xrn2 facilitates this pause-dependent termination by degrading the 3' product of poly(A) site cleavage. The human beta-actin gene also possesses poly(A) site proximal pause sequences, which like MAZ4 are G rich and promote transcriptional termination. Xrn2 depletion causes an increase in both steady-state RNA and Pol II levels downstream of the beta-actin poly(A) site. Taken together, we provide new insights into the mechanism of pause site-mediated termination and establish a general role for the 5'-->3' exonuclease Xrn2 in Pol II termination.

MeSH Terms
Actins/chemistry,genetics Base Sequence Blotting, Western Chromatin Immunoprecipitation DNA-Binding Proteins/genetics,metabolism Exoribonucleases/genetics,metabolism Globins/genetics HeLa Cells Humans Models, Genetic Molecular Sequence Data Plasmids/genetics RNA/analysis RNA Interference RNA Polymerase II/metabolism RNA Processing, Post-Transcriptional RNA, Messenger/metabolism Terminator Regions, Genetic Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
Actins DNA-Binding Proteins RNA, Messenger Transcription Factors c-MYC-associated zinc finger protein RNA Globins RNA Polymerase II Exoribonucleases XRN2 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gromak Natalia
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
West Steven
Proudfoot Nick J
References (39)
39 references, click to expand
  1. Products of in vitro cleavage and polyadenylation of simian virus 40 late pre-mRNAs.
    Mol Cell Biol. 1987 Apr;7(4):1518-29 PMID: 3037325
  2. Transcriptional termination and coupled polyadenylation in vitro.
    EMBO J. 2000 Jul 17;19(14):3770-7 PMID: 10899130
  3. Intergenic transcription and transinduction of the human beta-globin locus.
    Genes Dev. 1997 Oct 1;11(19):2494-509 PMID: 9334315
  4. Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):405-45 PMID: 10357856
  5. Human 5' --> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites.
    Nature. 2004 Nov 25;432(7016):522-5 PMID: 15565158
  6. Co-transcriptional commitment to alternative splice site selection.
    Nucleic Acids Res. 1998 Dec 15;26(24):5568-72 PMID: 9837984
  7. 5'-exonuclease-2 of Saccharomyces cerevisiae. Purification and features of ribonuclease activity with comparison to 5'-exonuclease-1.
    J Biol Chem. 1995 Jul 7;270(27):16063-9 PMID: 7608167
  8. MAZ elements alter transcription elongation and silencing of the fibroblast growth factor receptor 2 exon IIIb.
    J Biol Chem. 2004 Jul 9;279(28):29075-84 PMID: 15126509
  9. Quality control of mRNA 3'-end processing is linked to the nuclear exosome.
    Nature. 2001 Oct 4;413(6855):538-42 PMID: 11586364
  10. Pcf11 is a termination factor in Drosophila that dismantles the elongation complex by bridging the CTD of RNA polymerase II to the nascent transcript.
    Mol Cell. 2006 Jan 6;21(1):65-74 PMID: 16387654
  11. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription.
    Nature. 1997 Jan 23;385(6614):357-61 PMID: 9002523
  12. Strong polyadenylation and weak pausing combine to cause efficient termination of transcription in the human Ggamma-globin gene.
    Mol Cell Biol. 2005 Apr;25(8):3276-85 PMID: 15798211
  13. New perspectives on connecting messenger RNA 3' end formation to transcription.
    Curr Opin Cell Biol. 2004 Jun;16(3):272-8 PMID: 15145351
  14. Poly(A) signals control both transcriptional termination and initiation between the tandem GAL10 and GAL7 genes of Saccharomyces cerevisiae.
    EMBO J. 1998 Aug 17;17(16):4771-9 PMID: 9707436
  15. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation.
    Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8185-90 PMID: 12060763
  16. Definition of an efficient synthetic poly(A) site.
    Genes Dev. 1989 Jul;3(7):1019-25 PMID: 2570734
  17. MAZ-dependent termination between closely spaced human complement genes.
    EMBO J. 1994 Dec 1;13(23):5656-67 PMID: 7988563
  18. Transcriptional termination sequences in the mouse serum albumin gene.
    RNA. 2006 Apr;12(4):655-65 PMID: 16581808
  19. CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3'-end processing factor, Pcf11.
    Genes Dev. 2005 Jul 1;19(13):1572-80 PMID: 15998810
  20. RNA polymerase II transcription complexes may become arrested if the nascent RNA is shortened to less than 50 nucleotides.
    J Biol Chem. 2002 Sep 6;277(36):32527-37 PMID: 12087087
  21. Autocatalytic RNA cleavage in the human beta-globin pre-mRNA promotes transcription termination.
    Nature. 2004 Nov 25;432(7016):526-30 PMID: 15565159
  22. A functional mRNA polyadenylation signal is required for transcription termination by RNA polymerase II.
    Genes Dev. 1988 Apr;2(4):440-52 PMID: 2836265
  23. EM visualization of transcription by RNA polymerase II: downstream termination requires a poly(A) signal but not transcript cleavage.
    Mol Cell. 1999 Mar;3(3):379-87 PMID: 10198640
  24. RNA polymerase II is an essential mRNA polyadenylation factor.
    Nature. 1998 Sep 3;395(6697):93-6 PMID: 9738505
  25. Patterns of polyadenylation site selection in gene constructs containing multiple polyadenylation signals.
    Mol Cell Biol. 1988 Nov;8(11):4829-39 PMID: 2463466
  26. Terminal exon definition occurs cotranscriptionally and promotes termination of RNA polymerase II.
    Mol Cell. 1999 Mar;3(3):371-8 PMID: 10198639
  27. Characterization of the mouse beta maj globin transcription termination region: a spacing sequence is required between the poly(A) signal sequence and multiple downstream termination elements.
    Mol Cell Biol. 1993 Jan;13(1):578-87 PMID: 8417354
  28. Transcriptional termination between the closely linked human complement genes C2 and factor B: common termination factor for C2 and c-myc?
    EMBO J. 1991 Dec;10(13):4197-207 PMID: 1756727
  29. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination.
    Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452-6 PMID: 1502157
  30. Specific transcriptional pausing activates polyadenylation in a coupled in vitro system.
    Mol Cell. 1999 May;3(5):593-600 PMID: 10360175
  31. Termination of transcription in the mouse alpha-amylase gene Amy-2a occurs at multiple sites downstream of the polyadenylation site.
    Cell. 1984 Oct;38(3):737-44 PMID: 6091898
  32. The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II.
    Nature. 2004 Nov 25;432(7016):517-22 PMID: 15565157
  33. Independent functions of yeast Pcf11p in pre-mRNA 3' end processing and in transcription termination.
    EMBO J. 2003 May 1;22(9):2167-77 PMID: 12727883
  34. A pause site for RNA polymerase II is associated with termination of transcription.
    EMBO J. 1991 Jul;10(7):1833-42 PMID: 2050120
  35. How RNA polymerase II terminates transcription in higher eukaryotes.
    Trends Biochem Sci. 1989 Mar;14(3):105-10 PMID: 2658217
  36. Multiple transcript cleavage precedes polymerase release in termination by RNA polymerase II.
    Cell. 2001 Jun 1;105(5):669-81 PMID: 11389836
  37. Connecting transcription to messenger RNA processing.
    Trends Biochem Sci. 2000 Jun;25(6):290-3 PMID: 10838569
  38. Delay in synthesis of the 3' splice site promotes trans-splicing of the preceding 5' splice site.
    Mol Cell. 2005 Apr 15;18(2):245-51 PMID: 15837427
  39. Inefficient processing impairs release of RNA from the site of transcription.
    EMBO J. 1999 May 17;18(10):2855-66 PMID: 10329631
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.10.3986-3996.2006
Published
2006-05-00
Pages
3986-96
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1488997
Subset
IM
Grants
Medical Research Council · G9826944 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1128/MCB.26.10.3986-3996.2006 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2