Home LiteratureArticle Details
PMID: 2050120 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A pause site for RNA polymerase II is associated with termination of transcription.

The EMBO journal ·Vol. 10 ·No. 7 ·1991-07-00 ·Pages 1833-42

Enriquez-Harris P, Levitt N, Briggs D, Proudfoot NJ

Abstract

Termination of transcription by RNA polymerase II has been postulated to involve a pausing process. We have identified such a pause signal, 350 bp into the 3' flanking region of the human alpha 2 globin gene at a position where termination is thought to occur. We show that this pause signal enhances the utilization of an upstream poly(A) site which is otherwise out-competed by a stronger downstream poly(A) site. We also demonstrate that the pause site rescues a poly(A) site that is inactive due to its location within an intron. Using nuclear run-on analysis we show that elongating RNA polymerase II molecules accumulate over this pause signal. Furthermore we show that when the pause site is positioned immediately downstream of a strong poly(A) signal, significant levels of transcription termination take place.

MeSH Terms
Base Sequence Gene Expression Regulation Globins/genetics HeLa Cells Humans Introns Molecular Sequence Data Poly A/genetics RNA Polymerase II/genetics,metabolism Terminator Regions, Genetic Transcription, Genetic
Chemicals
Poly A Globins RNA Polymerase II
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Enriquez-Harris P
Sir William Dunn School of Pathology, University of Oxford, UK.
Levitt N
Briggs D
Proudfoot N J
References (42)
42 references, click to expand
  1. A termination site for Xenopus RNA polymerase I also acts as an element of an adjacent promoter.
    Cell. 1986 Dec 26;47(6):913-20 PMID: 3779846
  2. A transcription terminator located upstream of the mouse rDNA initiation site affects rRNA synthesis.
    Cell. 1986 Dec 26;47(6):901-11 PMID: 3779845
  3. Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process.
    Mol Cell Biol. 1986 Nov;6(11):4008-18 PMID: 3025624
  4. Purified RNA polymerase II recognizes specific termination sites during transcription in vitro.
    J Biol Chem. 1987 Jul 5;262(19):9098-108 PMID: 3036847
  5. 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 Dec;84(23):8306-10 PMID: 3479794
  6. Polyadenylation of mRNA precursors.
    Biochim Biophys Acta. 1988 May 6;950(1):1-12 PMID: 2896017
  7. Sequence requirements for premature termination of transcription in the human c-myc gene.
    Cell. 1988 Apr 22;53(2):245-56 PMID: 2834065
  8. A functional mRNA polyadenylation signal is required for transcription termination by RNA polymerase II.
    Genes Dev. 1988 Apr;2(4):440-52 PMID: 2836265
  9. Splice site selection dominates over poly(A) site choice in RNA production from complex adenovirus transcription units.
    EMBO J. 1988 Jul;7(7):2107-16 PMID: 3416835
  10. Intrinsic sites of transcription termination and pausing in the c-myc gene.
    Mol Cell Biol. 1988 Oct;8(10):4389-94 PMID: 3054517
  11. A rabbit beta-globin polyadenylation signal directs efficient termination of transcription of polyomavirus DNA.
    EMBO J. 1988 Aug;7(8):2515-22 PMID: 2847921
  12. RNA polymerase II is capable of pausing and prematurely terminating transcription at a precise location in vivo and in vitro.
    Proc Natl Acad Sci U S A. 1989 Jan;86(1):12-6 PMID: 2911563
  13. DNA sequences that mediate attenuation of transcription from the mouse protooncogene myc.
    Proc Natl Acad Sci U S A. 1989 Jan;86(2):505-9 PMID: 2463629
  14. A CCAAT box sequence in the adenovirus major late promoter functions as part of an RNA polymerase II termination signal.
    Cell. 1989 May 19;57(4):561-71 PMID: 2720783
  15. How RNA polymerase II terminates transcription in higher eukaryotes.
    Trends Biochem Sci. 1989 Mar;14(3):105-10 PMID: 2658217
  16. The transcription termination region of the adenovirus 2 major late transcript contains multiple functional elements.
    J Gen Virol. 1989 Jun;70 ( Pt 6):1337-45 PMID: 2659732
  17. Transcriptional termination between bovine papillomavirus type 1 (BPV-1) early and late polyadenylation sites blocks late transcription in BPV-1-transformed cells.
    J Virol. 1989 Aug;63(8):3529-34 PMID: 2545923
  18. Definition of an efficient synthetic poly(A) site.
    Genes Dev. 1989 Jul;3(7):1019-25 PMID: 2570734
  19. Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation.
    Proc Natl Acad Sci U S A. 1989 Oct;86(20):8024-8 PMID: 2813375
  20. RNA polymerase II transcription termination is mediated specifically by protein binding to a CCAAT box sequence.
    Mol Cell Biol. 1989 Nov;9(11):5254-9 PMID: 2601722
  21. The definition of a large viral transcription unit late in Ad2 infection of HeLa cells: mapping of nascent RNA molecules labeled in isolated nuclei.
    Cell. 1977 Apr;10(4):611-6 PMID: 862022
  22. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  23. The primary structure of the human epsilon-globin gene.
    Cell. 1980 Oct;21(3):621-6 PMID: 6254663
  24. The duplicated human alpha-globin genes: their relative expression as measured by RNA analysis.
    Cell. 1981 May;24(2):345-51 PMID: 7237552
  25. The organization, structure, and in vitro transcription of Alu family RNA polymerase III transcription units in the human alpha-like globin gene cluster: precipitation of in vitro transcripts by lupus anti-La antibodies.
    J Mol Appl Genet. 1982;1(4):343-60 PMID: 6286832
  26. alpha-Thalassemia caused by an unstable alpha-globin mutant.
    J Clin Invest. 1983 Mar;71(3):461-6 PMID: 6826718
  27. Termination of transcription in E. coli.
    Cell. 1983 Apr;32(4):1029-32 PMID: 6188534
  28. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
    Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 PMID: 6091052
  29. 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
  30. Transcription termination occurs within a 1000 base pair region downstream from the poly(A) site of the mouse beta-globin (major) gene.
    Nucleic Acids Res. 1984 Nov 26;12(22):8723-31 PMID: 6095210
  31. Termination of the ovalbumin gene transcription.
    EMBO J. 1984 Dec 1;3(12):2779-86 PMID: 6098444
  32. Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion.
    J Clin Invest. 1985 Sep;76(3):1057-64 PMID: 4044827
  33. Structural features of the murine dihydrofolate reductase transcription termination region: identification of a conserved DNA sequence element.
    Nucleic Acids Res. 1986 May 27;14(10):4113-25 PMID: 3714472
  34. Transcription boundaries of U1 small nuclear RNA.
    Mol Cell Biol. 1985 Sep;5(9):2332-40 PMID: 2942763
  35. Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation.
    Nature. 1986 Aug 7-13;322(6079):562-5 PMID: 3736674
  36. Translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes.
    J Clin Invest. 1986 Oct;78(4):1125-9 PMID: 3760187
  37. RNA polymerase II transcription terminates at a specific DNA sequence in a HeLa cell-free reaction.
    Proc Natl Acad Sci U S A. 1986 Oct;83(20):7623-7 PMID: 2429312
  38. Formation of the 3' end of U1 snRNA requires compatible snRNA promoter elements.
    Cell. 1986 Oct 24;47(2):249-58 PMID: 3768956
  39. 3' end formation of U1 snRNA precursors is coupled to transcription from snRNA promoters.
    Cell. 1986 Oct 24;47(2):259-66 PMID: 3021336
  40. Human alpha-globin gene expression. The dominant role of the alpha 2-locus in mRNA and protein synthesis.
    J Biol Chem. 1986 Nov 15;261(32):15327-33 PMID: 3771577
  41. A transcriptional terminator is a novel element of the promoter of the mouse ribosomal RNA gene.
    Cell. 1986 Dec 26;47(6):891-900 PMID: 3779844
  42. Alpha-thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3' end processing in the human alpha 2 globin gene.
    EMBO J. 1986 Nov;5(11):2915-22 PMID: 3024968
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-07-00
Pages
1833-42
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452858
Subset
IM
Grants
Wellcome Trust · United Kingdom
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