Home LiteratureArticle Details
PMID: 11604498 Published · ppublish English Journal Article

The transcription elongation factor CA150 interacts with RNA polymerase II and the pre-mRNA splicing factor SF1.

Molecular and cellular biology ·Vol. 21 ·No. 22 ·2001-11-00 ·Pages 7617-28

Goldstrohm AC, Albrecht TR, Suñé C, Bedford MT, Garcia-Blanco MA

Abstract

CA150 represses RNA polymerase II (RNAPII) transcription by inhibiting the elongation of transcripts. The FF repeat domains of CA150 bind directly to the phosphorylated carboxyl-terminal domain of the largest subunit of RNAPII. We determined that this interaction is required for efficient CA150-mediated repression of transcription from the alpha(4)-integrin promoter. Additional functional determinants, namely, the WW1 and WW2 domains of CA150, were also required for efficient repression. A protein that interacted directly with CA150 WW1 and WW2 was identified as the splicing-transcription factor SF1. Previous studies have demonstrated a role for SF1 in transcription repression, and we found that binding of the CA150 WW1 and WW2 domains to SF1 correlated exactly with the functional contribution of these domains for repression. The binding specificity of the CA150 WW domains was found to be unique in comparison to known classes of WW domains. Furthermore, the CA150 binding site, within the carboxyl-terminal half of SF1, contains a novel type of proline-rich motif that may be recognized by the CA150 WW1 and WW2 domains. These results support a model for the recruitment of CA150 to repress transcription elongation. In this model, CA150 binds to the phosphorylated CTD of elongating RNAPII and SF1 targets the nascent transcript.

MeSH Terms
Amino Acid Sequence Binding Sites Cell Line, Transformed DNA-Binding Proteins Gene Expression Regulation HeLa Cells Humans Molecular Sequence Data Phosphorylation Proline/metabolism RNA Polymerase II/metabolism RNA Precursors/metabolism RNA Splicing RNA Splicing Factors RNA-Binding Proteins/genetics,metabolism Repressor Proteins/genetics,metabolism Structure-Activity Relationship Trans-Activators/genetics,metabolism Transcription Factors Transcriptional Elongation Factors
Chemicals
DNA-Binding Proteins RNA Precursors RNA Splicing Factors RNA-Binding Proteins Repressor Proteins SF1 protein, human TCERG1 protein, human Trans-Activators Transcription Factors Transcriptional Elongation Factors Proline RNA Polymerase II
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Goldstrohm A C
Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Albrecht T R
Suñé C
Bedford M T
Garcia-Blanco M A
References (98)
98 references, click to expand
  1. Genomic organization of mouse gene zfp162.
    DNA Cell Biol. 1999 May;18(5):419-28 PMID: 10360842
  2. Transient interaction of BBP/ScSF1 and Mud2 with the splicing machinery affects the kinetics of spliceosome assembly.
    RNA. 1999 Jun;5(6):819-31 PMID: 10376880
  3. Transcriptional cofactor CA150 regulates RNA polymerase II elongation in a TATA-box-dependent manner.
    Mol Cell Biol. 1999 Jul;19(7):4719-28 PMID: 10373521
  4. The FF domain: a novel motif that often accompanies WW domains.
    Trends Biochem Sci. 1999 Jul;24(7):264-5 PMID: 10390614
  5. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH.
    Mol Cell. 2000 Jun;5(6):1067-72 PMID: 10912001
  6. Protein-interaction modules that organize nuclear function: FF domains of CA150 bind the phosphoCTD of RNA polymerase II.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9015-20 PMID: 10908677
  7. Converging on proline: the mechanism of WW domain peptide recognition.
    Nat Struct Biol. 2000 Aug;7(8):611-3 PMID: 10932238
  8. Structure of a WW domain containing fragment of dystrophin in complex with beta-dystroglycan.
    Nat Struct Biol. 2000 Aug;7(8):634-8 PMID: 10932245
  9. Structural basis for phosphoserine-proline recognition by group IV WW domains.
    Nat Struct Biol. 2000 Aug;7(8):639-43 PMID: 10932246
  10. Mediator of transcriptional regulation.
    Annu Rev Biochem. 2000;69:729-49 PMID: 10966474
  11. Coupled in vitro synthesis and splicing of RNA polymerase II transcripts.
    RNA. 2000 Sep;6(9):1325-34 PMID: 10999609
  12. Participation of the C-terminal domain of RNA polymerase II in exon definition during pre-mRNA splicing.
    Mol Cell Biol. 2000 Nov;20(21):8290-301 PMID: 11027297
  13. Orchestrated response: a symphony of transcription factors for gene control.
    Genes Dev. 2000 Oct 15;14(20):2551-69 PMID: 11040209
  14. Kinetic role for mammalian SF1/BBP in spliceosome assembly and function after polypyrimidine tract recognition by U2AF.
    J Biol Chem. 2000 Dec 1;275(48):38059-66 PMID: 10954700
  15. The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II.
    J Biol Chem. 2000 Dec 22;275(51):39935-43 PMID: 10978320
  16. Transcription of eukaryotic protein-coding genes.
    Annu Rev Genet. 2000;34:77-137 PMID: 11092823
  17. NeW wrinkles for an old domain.
    Cell. 2000 Dec 22;103(7):1001-4 PMID: 11163176
  18. Functions of WW domains in the nucleus.
    FEBS Lett. 2001 Feb 16;490(3):190-5 PMID: 11223034
  19. Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation.
    J Biol Chem. 2001 Mar 30;276(13):9978-84 PMID: 11266437
  20. Three protein factors (SF1, SF3 and U2AF) function in pre-splicing complex formation in addition to snRNPs.
    EMBO J. 1991 Jun;10(6):1503-9 PMID: 1827409
  21. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat.
    J Virol. 1992 Jan;66(1):139-49 PMID: 1727476
  22. Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains.
    EMBO J. 1996 Mar 1;15(5):1045-54 PMID: 8605874
  23. Three functional classes of transcriptional activation domain.
    Mol Cell Biol. 1996 May;16(5):2044-55 PMID: 8628270
  24. The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins.
    Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6975-80 PMID: 8692929
  25. A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8253-7 PMID: 8710856
  26. Reversible phosphorylation of the C-terminal domain of RNA polymerase II.
    J Biol Chem. 1996 Aug 9;271(32):19009-12 PMID: 8759772
  27. Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide.
    Nature. 1996 Aug 15;382(6592):646-9 PMID: 8757138
  28. Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA.
    RNA. 1996 Aug;2(8):794-810 PMID: 8752089
  29. The structure and function of proteins involved in mammalian pre-mRNA splicing.
    Annu Rev Biochem. 1996;65:367-409 PMID: 8811184
  30. Multiple nuclear regulatory proteins bind a single cis-acting promoter element to control basal transcription of the human alpha 4 integrin gene in corneal epithelial cells.
    DNA Cell Biol. 1996 Sep;15(9):779-92 PMID: 8836036
  31. The general transcription factors of RNA polymerase II.
    Genes Dev. 1996 Nov 1;10(21):2657-83 PMID: 8946909
  32. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription.
    Nature. 1997 Jan 23;385(6614):357-61 PMID: 9002523
  33. A functional interaction between the carboxy-terminal domain of RNA polymerase II and pre-mRNA splicing.
    J Cell Biol. 1997 Jan 13;136(1):5-18 PMID: 9008699
  34. Splicing factors associate with hyperphosphorylated RNA polymerase II in the absence of pre-mRNA.
    J Cell Biol. 1997 Jan 13;136(1):19-28 PMID: 9008700
  35. RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo.
    Mol Cell. 1999 Jun;3(6):697-705 PMID: 10394358
  36. Mechanism and regulation of transcriptional elongation by RNA polymerase II.
    Curr Opin Cell Biol. 1999 Jun;11(3):342-6 PMID: 10395562
  37. Coupling RNA polymerase II transcription with pre-mRNA processing.
    Curr Opin Cell Biol. 1999 Jun;11(3):347-51 PMID: 10395561
  38. mRNA polyadenylation and its coupling to other RNA processing reactions and to transcription.
    Curr Opin Cell Biol. 1999 Jun;11(3):352-7 PMID: 10395555
  39. HIV-1 Tat protein promotes formation of more-processive elongation complexes.
    EMBO J. 1991 Dec;10(13):4189-96 PMID: 1756726
  40. Contribution of the TATA motif to Tat-mediated transcriptional activation of human immunodeficiency virus gene expression.
    J Virol. 1992 Sep;66(9):5594-7 PMID: 1501293
  41. Purification of splicing factor SF1, a heat-stable protein that functions in the assembly of a presplicing complex.
    Mol Cell Biol. 1992 Oct;12(10):4545-52 PMID: 1406644
  42. The human immunodeficiency virus type 1 long terminal repeat specifies two different transcription complexes, only one of which is regulated by Tat.
    J Virol. 1993 Apr;67(4):1752-60 PMID: 8445708
  43. Positive patches and negative noodles: linking RNA processing to transcription?
    Trends Biochem Sci. 1993 Apr;18(4):117-9 PMID: 8493720
  44. Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with transcription.
    Cell. 1994 Jan 14;76(1):183-92 PMID: 8287477
  45. An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter.
    J Biol Chem. 1994 Jun 3;269(22):15652-60 PMID: 8195215
  46. Transcriptional elongation by RNA polymerase II is stimulated by transactivators.
    Cell. 1994 Jun 3;77(5):749-59 PMID: 8205623
  47. Multiple regulatory elements control the basal promoter activity of the human alpha 4 integrin gene.
    DNA Cell Biol. 1994 Nov;13(11):1071-85 PMID: 7702751
  48. Cloning and characterization of the promoter region of the murine alpha-4 integrin subunit.
    DNA Cell Biol. 1994 Jul;13(7):743-54 PMID: 7772255
  49. Regulation of transcriptional elongation by RNA polymerase II.
    Curr Opin Genet Dev. 1995 Apr;5(2):210-6 PMID: 7613091
  50. A protein-RNA interaction network facilitates the template-independent cooperative assembly on RNA polymerase of a stable antitermination complex containing the lambda N protein.
    Genes Dev. 1995 Nov 15;9(22):2831-45 PMID: 7590257
  51. Structural organization of transcription termination factor Rho.
    J Biol Chem. 1996 Jan 19;271(3):1251-4 PMID: 8576105
  52. Direct evidence that HIV-1 Tat stimulates RNA polymerase II carboxyl-terminal domain hyperphosphorylation during transcriptional elongation.
    J Mol Biol. 1999 Jul 30;290(5):929-41 PMID: 10438593
  53. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme.
    Mol Cell. 1999 Jul;4(1):123-8 PMID: 10445034
  54. HIV-1 Tat: coping with negative elongation factors.
    Curr Opin Immunol. 1999 Aug;11(4):460-5 PMID: 10448148
  55. Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer.
    Mol Cell. 1999 Aug;4(2):251-8 PMID: 10488340
  56. ATP can be dispensable for prespliceosome formation in yeast.
    Genes Dev. 2000 Jan 1;14(1):97-107 PMID: 10640279
  57. Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection.
    Immunity. 2000 Jan;12(1):61-70 PMID: 10661406
  58. A yeast heterogeneous nuclear ribonucleoprotein complex associated with RNA polymerase II.
    Genetics. 2000 Feb;154(2):557-71 PMID: 10655211
  59. Transcription elongation factor SII.
    Bioessays. 2000 Apr;22(4):327-36 PMID: 10723030
  60. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II.
    Mol Cell Biol. 2000 Apr;20(8):2629-34 PMID: 10733565
  61. A novel pro-Arg motif recognized by WW domains.
    J Biol Chem. 2000 Apr 7;275(14):10359-69 PMID: 10744724
  62. A dual role for BBP/ScSF1 in nuclear pre-mRNA retention and splicing.
    EMBO J. 2000 Apr 17;19(8):1873-86 PMID: 10775271
  63. Structural analysis of WW domains and design of a WW prototype.
    Nat Struct Biol. 2000 May;7(5):375-9 PMID: 10802733
  64. Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains.
    J Biol Chem. 2000 May 26;275(21):16030-6 PMID: 10748127
  65. RNA polymerase II and the integration of nuclear events.
    Genes Dev. 2000 Jun 15;14(12):1415-29 PMID: 10859161
  66. Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription.
    Mol Cell Biol. 2000 Jul;20(14):5077-86 PMID: 10866664
  67. Transcription elongation and human disease.
    Annu Rev Biochem. 1999;68:301-19 PMID: 10872452
  68. Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II.
    J Biol Chem. 2000 Jul 7;275(27):20562-71 PMID: 10781604
  69. Structure and function of the WW domain.
    Prog Biophys Mol Biol. 1996;65(1-2):113-32 PMID: 9029943
  70. RNA polymerase slides home: pause and termination site recognition.
    Cell. 1997 Mar 21;88(6):741-4 PMID: 9118216
  71. Mechanism and regulation of transcriptional elongation and termination by RNA polymerase II.
    Curr Opin Genet Dev. 1997 Apr;7(2):199-204 PMID: 9115429
  72. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals.
    Cell. 1997 May 2;89(3):403-12 PMID: 9150140
  73. Pre-mRNA processing and the CTD of RNA polymerase II: the tail that wags the dog?
    Cell. 1997 May 16;89(4):491-4 PMID: 9160740
  74. FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich ligands.
    EMBO J. 1997 May 1;16(9):2376-83 PMID: 9171351
  75. The splicing factor BBP interacts specifically with the pre-mRNA branchpoint sequence UACUAAC.
    Cell. 1997 May 30;89(5):781-7 PMID: 9182766
  76. Basic mechanisms of transcript elongation and its regulation.
    Annu Rev Biochem. 1997;66:117-72 PMID: 9242904
  77. CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription.
    Mol Cell Biol. 1997 Oct;17(10):6029-39 PMID: 9315662
  78. Functional association between promoter structure and transcript alternative splicing.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11456-60 PMID: 9326631
  79. Transcription units as RNA processing units.
    Genes Dev. 1997 Dec 15;11(24):3279-85 PMID: 9407022
  80. Human ZFM1 protein is a transcriptional repressor that interacts with the transcription activation domain of stage-specific activator protein.
    J Biol Chem. 1998 Mar 20;273(12):6868-77 PMID: 9506990
  81. A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition.
    Genes Dev. 1998 Mar 15;12(6):858-67 PMID: 9512519
  82. Conservation of functional domains involved in RNA binding and protein-protein interactions in human and Saccharomyces cerevisiae pre-mRNA splicing factor SF1.
    RNA. 1998 May;4(5):551-65 PMID: 9582097
  83. Diverse modes of alternative splicing of human splicing factor SF1 deduced from the exon-intron structure of the gene.
    Gene. 1998 Apr 28;211(1):29-37 PMID: 9573336
  84. Transcriptional activation domains stimulate initiation and elongation at different times and via different residues.
    EMBO J. 1998 Jun 1;17(11):3146-54 PMID: 9606196
  85. Molecular genetics of the RNA polymerase II general transcriptional machinery.
    Microbiol Mol Biol Rev. 1998 Jun;62(2):465-503 PMID: 9618449
  86. The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription.
    J Biol Chem. 1998 Jul 17;273(29):18086-91 PMID: 9660765
  87. The KH domain of the branchpoint sequence binding protein determines specificity for the pre-mRNA branchpoint sequence.
    RNA. 1998 Aug;4(8):998-1006 PMID: 9701290
  88. CUS2, a yeast homolog of human Tat-SF1, rescues function of misfolded U2 through an unusual RNA recognition motif.
    Mol Cell Biol. 1998 Sep;18(9):5000-9 PMID: 9710584
  89. WW domain-mediated interactions reveal a spliceosome-associated protein that binds a third class of proline-rich motif: the proline glycine and methionine-rich motif.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10602-7 PMID: 9724750
  90. Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex.
    Nat Genet. 1998 Sep;20(1):46-50 PMID: 9731529
  91. Transcriptional regulation of the alpha 4 integrin subunit gene in the metastatic spread of uveal melanoma.
    Anticancer Res. 1998 Sep-Oct;18(5A):3539-47 PMID: 9858937
  92. Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro.
    EMBO J. 1998 Dec 15;17(24):7395-403 PMID: 9857195
  93. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation.
    Mol Cell. 1999 Jan;3(1):109-18 PMID: 10024884
  94. Tat-associated kinase (P-TEFb): a component of transcription preinitiation and elongation complexes.
    J Biol Chem. 1999 Mar 12;274(11):7399-404 PMID: 10066804
  95. Structure and function of the human transcription elongation factor DSIF.
    J Biol Chem. 1999 Mar 19;274(12):8085-92 PMID: 10075709
  96. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation.
    Cell. 1999 Apr 2;97(1):41-51 PMID: 10199401
  97. A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.
    EMBO J. 1999 May 4;18(9):2551-62 PMID: 10228168
  98. Phosphorylated RNA polymerase II stimulates pre-mRNA splicing.
    Genes Dev. 1999 May 15;13(10):1234-9 PMID: 10346811
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.22.7617-7628.2001
Published
2001-11-00
Pages
7617-28
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC99933
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.22.7617-7628.2001 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