Skip to main content
SpringerLink
Log in

Constitutive Transport Element-Mediated Nuclear Export

  • Chapter
Nuclear Export of Viral RNAs

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 259))

Abstract

The molecular biology of retrovirus replication and gene regulation has been intensely analyzed for many years. These studies have made it clear that retroviral expression is controlled not only at the transcriptional level, but also by posttranscriptional mechanisms that regulate the export of RNA from the host cell nucleus to the cytoplasm. This involves the action of proteins that actively shuttle between the nucleus and cytoplasm using specific nuclear import and export signals. Thus retroviruses have become important model systems for nucleo-cytoplasmic trafficking (for previous reviews, see Hammarskjold 1997; Gullen 1998; Pollard and Malim 1998)

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Askjaer P, Bachi A, Wilm M, Bischoff FR, Weeks DL, Ogniewski V, Ohno M, Niehrs C, Kjems J, Mattaj IW, et al. (1999) RanGTP-regulated interactions of CRM 1 with nucleoporins and a shuttling DEAD-box helicase. Mol Cell Biol 19:6276–6285

    PubMed  CAS  Google Scholar 

  • Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J (1998) The specificity of the CRM 1-Rev nuclear export signal interaction is mediated by RanGTP. J Biol Chem 273:33414–33422

    Article  PubMed  CAS  Google Scholar 

  • Bachi A, Braun IC, Rodrigues JP, Pante N, Ribbeck K, von Kobbe C, Kutay U, Wilm M, Gorlich D, Carmo-Fonseca M, et al. (2000) The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates. RNA 6:136–158

    Article  PubMed  CAS  Google Scholar 

  • Bear J, Tan W, Zolotukhin AS, Tabernero C, Hudson EA, Felber BK (1999) Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs. Mol Cell Biol 19:6306–6317

    PubMed  CAS  Google Scholar 

  • Black BE, Levesque L, Holaska JM, Wood TC, Paschal BM (1999) Identification of an NTF2-related factor that binds Ran-GTP and regulates nuclear protein export. Mol Cell Biol 19:8616–8624

    PubMed  CAS  Google Scholar 

  • Bolodeoku J, Yoshida K, Sugino T, Goodison S, Tarin D (1996) Accumulation of immature introncontaining CD44 gene transcripts in breast cancer tissues. Mol Diagn 1:175–181

    Article  PubMed  CAS  Google Scholar 

  • Braun IC, Rohrbach E, Schmitt C, Izaurralde E (1999) TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus. EMBO J 18:1953–1965

    Article  PubMed  CAS  Google Scholar 

  • Bray M, Prasad S, Dubay JW, Hunter E, Jeang KT, Rekosh D, Hammarskjöld ML (1994) A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sei USA 91:1256–1260

    Article  CAS  Google Scholar 

  • Carmo-Fonseca M, Custodio N, Calado A (1999) Intranuclear trafficking of messenger RNA. Crit Rev Eukaryot Gene Expr 9:213–219

    Article  PubMed  CAS  Google Scholar 

  • Chang DD, Sharp PA (1989) Regulation by HIV Rev depends upon recognition of splice sites. Cell 59:789–795

    Article  PubMed  CAS  Google Scholar 

  • Corbett AH, Silver PA (1996) The NTF2 gene encodes an essential, highly conserved protein that functions in nuclear transport in vivo. J Biol Chem 271:18477–18484

    Article  PubMed  CAS  Google Scholar 

  • Gullen BR (1998) Retroviruses as model systems for the study of nuclear RNA export pathways. Virology 249:203–210

    Article  Google Scholar 

  • D’Agostino DM, Felber BK, Harrison JE, Pavlakis GN (1992) The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs. Mol Cell Biol 12:1375–1386

    PubMed  Google Scholar 

  • Deed RW, Jasiok M, Norton JD (1996) Attenuated function of a variant form of the helix-loop-helix protein, Id-3, generated by an alternative splicing mechanism. FEBS Lett 393:113–116

    Article  PubMed  CAS  Google Scholar 

  • Emerman M, Vazeux R, Peden K (1989) The rev gene product of the human immunodeficiency virus aff’ects envelope-specific RNA localization. Cell 57:1155–1165

    Article  PubMed  CAS  Google Scholar 

  • Ernst R, Bray M, Rekosh D, Hammarskjöld M-L (1997a) A structured retroviral RNA element that mediates nucleocytoplasmic export of intron-containing RNA. Mol Cell Biol 17:135–144

    PubMed  CAS  Google Scholar 

  • Ernst RK, Bray M, Rekosh D, Hammarskjöld ML (1997b) Secondary structure and mutational analysis of the Mason-Pfizer monkey virus RNA constitutive transport element. RNA 3:210–222

    PubMed  CAS  Google Scholar 

  • Felber BK, Hadzopoulou-Cladaras M, Cladaras C, Copeland T, Pavlakis GN (1989) Rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sei USA 86:1496–1499

    Article  Google Scholar 

  • Fischer U, Huber J, Boelens WC, Mattaj IW, Luhrmann R (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82:475–483

    Article  PubMed  CAS  Google Scholar 

  • Fischer U, Meyer S, Teufel M, Heckel C, Luhrmann R, Rautmann G (1994) Evidence that HIV-1 Rev directly promotes the nuclear export of unspliced RNA. EMBO J 13:4105–4112

    PubMed  CAS  Google Scholar 

  • Fischer U, Pollard VW, Luhrmann R, Teufel M, Michael MW, Dreyfuss G, Malim MH (1999) Rev-mediated nuclear export of RNA is dominant over nuclear retention and is coupled to the Ran-GTPase cycle. Nucleic Acids Res 27:4128–4134

    Article  PubMed  CAS  Google Scholar 

  • Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997) CRMl is an export receptor for leucine-rich nuclear export signals. Cell 90:1051–1060

    Article  PubMed  CAS  Google Scholar 

  • Fornerod M, van Deursen J, van Baal S, Reynolds A, Davis D, Murti KG, Fransen J, Grosveld G (1997) The human homologue of yeast CRMl is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. EMBO J 16:807–816

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli S, Totty NF, Hsuan JJ, Courtneidge SA (1994) A target for Src in mitosis. Nature 368:871–874

    Article  PubMed  CAS  Google Scholar 

  • Goodison S, Yoshida K, Churchman M, Tarin D (1998) Multiple intron retention occurs in tumor cell CD44 mRNA processing. Am J Pathol 153:1221–1228

    Article  PubMed  CAS  Google Scholar 

  • Gorham H, Woodman A, Goodison S, Marsh J, Charnock M, Manek S, Sugino T, Tarin D (1999) CD44 expression in cervical intraepithelial neoplasia (CIN) and carcinoma. Mol Diagn 4:45–56

    Article  PubMed  CAS  Google Scholar 

  • Gorlich D, Kutay U (1999) Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol 15:607–660

    Article  PubMed  CAS  Google Scholar 

  • Gruter P, Tabernero C, von KC, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E (1998) TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell 1:649–659

    Article  PubMed  CAS  Google Scholar 

  • Guzik B, Prasad S, Levesque L, Black BE, Paschal BM, Rekosh D, Hammarskjöld M-L (2001) NXTl/ pi5 is a crucial cellular cofactor in TAP mediated export of intron-containing RNA in mammahan cells. Mol Cell Biol (in press)

    Google Scholar 

  • Hammarskjöld M-L (1997) Regulation of retroviral RNA export. Sem in Cell Dev Bio 8:83–90

    Article  Google Scholar 

  • Hammarskjöld M-L, Heimer J, Hammarskjöld B, Sangwan I, Albert L, Rekosh D (1989) Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol 63:1959–1966

    PubMed  Google Scholar 

  • Hammarskjöld ML, Li H, Rekosh D, Prasad S (1994) Human immunodeficiency virus env expression becomes Rev-independent if the env region is not defined as an intron. J Virol 68:951–958

    PubMed  Google Scholar 

  • lacampo S, Cochrane A (1996) Human immunodeficiency virus type 1 Rev function requires continued synthesis of its target mRNA. J Virol 70:8332–8339

    Google Scholar 

  • Jan E, Motzny CK, Graves LE, Goodwin EB (1999) The STAR protein, GLD-l, is a translational regulator of sexual identity in Cacuorhabditis elegcms. EMBO J 18:258–269

    Article  PubMed  CAS  Google Scholar 

  • Jarmolowski A, Boelens WC, Izaurralde E, Mattaj IW (1994) Nuclear export of different classes of RNA is mediated by specific factors. J Cell Biol 124:627–635

    Article  PubMed  CAS  Google Scholar 

  • Kang Y, Bogerd HP, Yang J, Gullen BR (1999) Analysis of the RNA binding specificity of the human tap protein, a constitutive transport element-specific nuclear RNA export factor. Virology 262:200–209

    Article  PubMed  CAS  Google Scholar 

  • Kang Y, Gullen BR (1999) The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Dev 13:1126–1139

    Article  PubMed  CAS  Google Scholar 

  • Katahira J, Strasser K, Podtelejnikov A, Mann M, Jung JU, Hurt E (1999) The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J 18:2593–2609

    Article  PubMed  CAS  Google Scholar 

  • Lawrence JB, Cochrane AW, Johnson CV, Perkins A, Rosen CA (1991) The HIV-1 Rev protein: a model system for coupled RNA transport and translation. New Biol 3:1220–1232

    PubMed  CAS  Google Scholar 

  • Le Hir H, Moore MJ, Maquat LE (2000) Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at cxon-exon junctions. Genes Dev 14:1098–1108

    PubMed  Google Scholar 

  • Legrain P, Rosbash M (1989) Some eis-and trans-acting mutants for splicing target pre-mRNA to the cytoplasm. Cell 57:573–583

    Article  PubMed  CAS  Google Scholar 

  • Li J, Tang H, Mullen TM, Westberg C, Reddy TR, Rose DW, Wong-Staal F (1999) A role for RNA helicase A in post-transcriptional regulation of HIV type I. Proc Natl Acad Sei USA 96:709–714

    Article  CAS  Google Scholar 

  • Lock P, Fumagalli S, Polakis P, McCormick F. Courtneidge SA (1996) The human p62 cDNA encodes Sam68 and not the RasGAP-associated p62 protein. Cell 84:23–24

    Google Scholar 

  • Lu XB, Heimer J, Rekosh D, Hammarskjöld ML (1990) Ul small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. Proc Natl Acad Sei USA 87:7598 7602

    Google Scholar 

  • Luo MJ, Reed R (1999) Splicing is required for rapid and efficient mRNA export in metazoans. Proc Natl Acad Sei USA 96:14937–14942

    Article  CAS  Google Scholar 

  • Malim MH, Gullen BR (1993) Rev and the fate of pre-mRNA in the nucleus: implications for the regulation of RNA processing in eukaryotes. Mol Cell Biol 13:6180 6189

    PubMed  Google Scholar 

  • Malim MH, Hauber J, Le SV, Maizel JV, Gullen BR (1989) The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338:254–257

    Article  PubMed  CAS  Google Scholar 

  • Mattaj IW, Englmeier L (1998) Nucleocytoplasmic transport: the soluble phase. Annu Rev Biochem 67:265–306

    Article  PubMed  CAS  Google Scholar 

  • Moroianu J (1999) Nuclear import and export: transport factors, mechanisms and regulation. Grit Rev Eukaryot Gene Expr 9:89–106

    Article  CAS  Google Scholar 

  • Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD, Montminy M (1997) RNA helicase A mediates association of GBP with RNA polymerase 11. Cell 90:1107–1112

    Article  PubMed  CAS  Google Scholar 

  • Nakielny S, Dreyfuss G (1999) Transport of proteins and RNAs in and out of the nucleus. Cell 99:677–690

    Article  PubMed  CAS  Google Scholar 

  • Nakielny S, Fischer U, Michael WM, Dreyfuss G (1997) RNA transport. Annu Rev Neurosci 20:269–301

    Article  PubMed  CAS  Google Scholar 

  • Nehlin JO, Hara E, Kuo WL, Collins C, Campisi J (1997) Genomic organization, sequence, and chromosomal localization of the human helix-loop-helix Idl gene. Biochem Biophys Res Commun 231:628–634

    Article  PubMed  CAS  Google Scholar 

  • Ogert RA, Beemon KL (1998) Mutational analysis of the rous sarcoma virus DR posttranscriptional control element. J Virol 72:3407–3411

    PubMed  CAS  Google Scholar 

  • Ogert RA, Lee LH, Beemon KL (1996) Avian retroviral RNA element promotes unspliced RNA accumulation in the cytoplasm. J Virol 70:3834–3843

    PubMed  CAS  Google Scholar 

  • Ohno M, Segref A, Bachi A, Wilm M, Mattaj IW (2000) PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation. Cell 101:187–198

    Article  PubMed  CAS  Google Scholar 

  • Olsen HS, Cochrane AW, Rosen C (1992) Interaction of cellular factors with intragenic cw-acting repressive sequences within the HIV genome. Virology 191:709–715

    Article  PubMed  CAS  Google Scholar 

  • Paschal BM, Delphin C, Gerace L (1996) Nucleotide-specific interaction of Ran/TC4 with nuclear transport factors NTF2 and p97. Proc Natl Acad Sei USA 93:7679–7683

    Article  CAS  Google Scholar 

  • Pasquinelli AE, Ernst RK, Lund E, Grimm C, Zapp ML, Rekosh D, Hammarskjöld ML, Dahlberg JE (1997) The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. EMBO J 16:7500–7510

    Article  PubMed  CAS  Google Scholar 

  • Pollard VW, Malim MH (1998) The HIV-1 Rev protein. Annu Rev Microbiol 52:491–532

    Article  PubMed  CAS  Google Scholar 

  • Prasad J, Colwill K, Pawson T, Manley JL (1999) The protein kinase Clk/Sty directly modulates SR protein activity: both hyper-and hypophosphorylation inhibit splicing. Mol Cell Biol 19:6991–7000

    PubMed  CAS  Google Scholar 

  • Reddy TR, Xu W, Mau JK, Goodwin CD, Suhasini M, Tang H, Frimpong K, Rose DW, Wong-Staal F (1999) Inhibition of HIV replication by dominant negative mutants of Sam68, a functional homolog of HIV-1 Rev. Nat Med 5:635–642

    Article  PubMed  CAS  Google Scholar 

  • Rizvi TA, Schmidt RD, Lew KA (1997) Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) functions in a position-dependent manner. Virology 236:118–129

    Article  PubMed  CAS  Google Scholar 

  • Saavedra C, Felber B, Izaurralde E (1997) The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export. Curr Biol 7:619–628

    Article  PubMed  CAS  Google Scholar 

  • Saccomanno L, Loushin C, Jan E, Punkay E, Artzt K, Goodwin EB (1999) The STAR protein QKI-6 is a translational repressor. Proc Natl Acad Sei USA 96:12605–12610

    Article  CAS  Google Scholar 

  • Segref A, Sharma K, Doye V, Hellwig A, Huber J, Luhrmann R, Hurt E (1997) Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. EMBO J 16:3256–3271

    Article  PubMed  CAS  Google Scholar 

  • Simpson SB, Zhang L, Craven RC, Stoltzfus CM (1997) Rous sarcoma virus direct repeat eis elements exert effects at several points in the virus life cycle. J Virol 71:9150–9156

    PubMed  CAS  Google Scholar 

  • Springhorn JP, Singh K, Kelly RA, Smith TW (1994) Posttranscriptional regulation of Idl activity in cardiac muscle. Alternative splicing of novel Idl transcript permits homodimerization. J Biol Chem 269:5132–5136

    PubMed  CAS  Google Scholar 

  • Stickeler E, Mobus VJ, Kieback DG, Kohlberger P, Runnebaum IB, Kreienberg R (1997) Intron 9 retention in gene transcripts suggests involvement of CD44 in the tumorigenesis of ovarian cancer. Anticancer Res 17:4395–4398

    PubMed  CAS  Google Scholar 

  • Stojdl DF, Bell JC (1999) SR protein kinases: the splice of life. Biochem Cell Biol 77:293–298

    Article  PubMed  CAS  Google Scholar 

  • Tabernero C, Zolotukhin AS, Bear J, Schneider R, Karsenty G, Felber BK (1997) Identification of an RNA sequence within an intracisternal-A particle element able to replace Rev-mediated posttrans-criptional regulation of human immunodeficiency virus type 1. J Virol 71:95–101

    PubMed  CAS  Google Scholar 

  • Tabernero C, Zolotukhin AS, Valentin A, Pavlakis GN, Felber BK (1996) The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function. J Virol 70:5998–6011

    PubMed  CAS  Google Scholar 

  • Tang H, Gaietta GM, Fischer WH, Ellisman MH, Wong-Staal F (1997) A cellular cofactor for the constitutive transport element of type D retrovirus. Science 276:1412–1415

    Article  PubMed  CAS  Google Scholar 

  • Tang H, Xu Y, Wong-Staal F (1997) Identification and purification of cellular proteins that specifically interact with the RNA constitutive transport elements from retrovirus D. Virology 228:333–339

    Article  PubMed  CAS  Google Scholar 

  • Taylor SJ, Shalloway D (1994) An RNA-binding protein associated with Src through its SH2 and SH3 domains in mitosis. Nature 368:867–871

    Article  PubMed  CAS  Google Scholar 

  • Truant R, Kang Y, Gullen BR (1999) The human tap nuclear RNA export factor contains a novel transportin-dependent nuclear localization signal that lacks nuclear export signal function. J Biol Chem 274:32167–32171

    Article  PubMed  CAS  Google Scholar 

  • Wodrich H, Schambach A, Krausslich HG (2000) Multiple copies of the Mason-Pfizer monkey virus constitutive RNA transport element lead to enhanced HIV-1 Gag expression in a context-dependent manner. Nucleic Acids Res 28:901–910

    Article  PubMed  CAS  Google Scholar 

  • Wolff B, Sanglier JJ, Wang Y (1997) Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem Biol 4:139–147

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Cullen BR (1999) Structural and functional analysis of the avian leukemia virus constitutive transport element. RNA 5:1645–1655

    Article  PubMed  CAS  Google Scholar 

  • Yeakley JM, Tronchere H, Olesen J, Dyck JA, Wang HY, Pu XD (1999) Phosphorylation regulates in vivo interaction and molecular targeting of serine/arginine-rich pre-mRNA splicing factors. J Cell Biol 145:447–455

    Article  PubMed  CAS  Google Scholar 

  • Yoon DW, Lee H, Seol W, DeMaria M, Rosenzweig M, Jung JU (1997) Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. Immunity 6:571–582

    Article  PubMed  CAS  Google Scholar 

  • Yoshida K, Bolodeoku J, Sugino T, Goodison S, Matsumura Y, Warren BF, Toge T, Tahara E, Tarin D (1995) Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors. Cancer Res 55:4273–4277

    PubMed  CAS  Google Scholar 

  • Zhang G, Zapp ML, Yan G, Green MR (1996) Localization of HIV-1 RNA in mammalian nuclei. J Cell Biol 135:9–18

    Article  PubMed  CAS  Google Scholar 

  • Zolotukhin AS, Valentin A, Pavlakis GN, Felber BK (1994) Continuous propagation of RRE(−) and Rev(−)RRE(−) human immunodeficiency virus type 1 molecular clones containing a cis-acting element of simian retrovirus type 1 in human peripheral blood lymphocytes. J Virol 68:7944 7952

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Myles H. Thaler Center for AIDS and Human Retrovirus Research and the Department of Microbiology, University of Virginia, Charlottesville, VA, 22908, USA

    M.-L. Hammarskjöld

Authors
  1. M.-L. Hammarskjöld
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany

    Joachim Hauber

  2. Dept. of Molecular and Experimental Medicine, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Peter K. Vogt

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hammarskjöld, ML. (2001). Constitutive Transport Element-Mediated Nuclear Export. In: Hauber, J., Vogt, P.K. (eds) Nuclear Export of Viral RNAs. Current Topics in Microbiology and Immunology, vol 259. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56597-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-56597-7_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62522-0

  • Online ISBN: 978-3-642-56597-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation