, Volume 117, Issue 4, pp 319–331 | Cite as

Biogenesis of mRNPs: integrating different processes in the eukaryotic nucleus

  • Rosa Luna
  • Hélène Gaillard
  • Cristina González-Aguilera
  • Andrés AguileraEmail author


Transcription is a central function occurring in the nucleus of eukaryotic cells in coordination with other nuclear processes. During transcription, the nascent pre-mRNA associates with mRNA-binding proteins and undergoes a series of processing steps, resulting in export-competent mRNA ribonucleoprotein complexes (mRNPs) that are transported into the cytoplasm. Experimental evidence increasingly indicates that the different processing steps (5′-end capping, splicing, 3′-end cleavage) and mRNP export are connected to each other as well as to transcription, both functionally and physically. Here, we review the overall process of mRNP biogenesis with particular emphasis on the functional coupling of transcription with mRNP biogenesis and export and its relationship to nuclear organization.


Nuclear Pore Complex Nuclear Periphery Transcription Elongation mRNA Export Exon Junction Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank J.C. Reyes for critical reading of the manuscript and D. Haun for style supervision. Research in A.A.’s lab is funded by grants from the Spanish Ministry of Science and Education (BFU2006-05260 and Consolider Ingenio 2010 CDS2007-0015) and from the Junta de Andalucia (CVI102 and CVI624).


  1. Abruzzi KC, Lacadie S, Rosbash M (2004) Biochemical analysis of TREX complex recruitment to intronless and intron-containing yeast genes. EMBO J 23:2620–2631PubMedGoogle Scholar
  2. Abruzzi KC, Belostotsky DA, Chekanova JA, Dower K, Rosbash M (2006) 3′-End formation signals modulate the association of genes with the nuclear periphery as well as mRNP dot formation. EMBO J 25:4253–4262PubMedGoogle Scholar
  3. Aguilera A (2005) Cotranscriptional mRNP assembly: from the DNA to the nuclear pore. Curr Opin Cell Biol 17:242–250PubMedGoogle Scholar
  4. Ahmed S, Brickner JH (2007) Regulation and epigenetic control of transcription at the nuclear periphery. Trends Genet 23:396–402PubMedGoogle Scholar
  5. Ahn SH, Kim M, Buratowski S (2004) Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3′ end processing. Mol Cell 13:67–76PubMedGoogle Scholar
  6. Akhtar A, Gasser SM (2007) The nuclear envelope and transcriptional control. Nat Rev Genet 8:507–517PubMedGoogle Scholar
  7. Anderson JT, Wilson SM, Datar KV, Swanson MS (1993) NAB2: a yeast nuclear polyadenylated RNA-binding protein essential for cell viability. Mol Cell Biol 13:2730–2741PubMedGoogle Scholar
  8. Andrulis ED, Guzman E, Doring P, Werner J, Lis JT (2000) High-resolution localization of Drosophila Spt5 and Spt6 at heat shock genes in vivo: roles in promoter proximal pausing and transcription elongation. Genes Dev 14:2635–2649PubMedGoogle Scholar
  9. Ansari A, Hampsey M (2005) A role for the CPF 3′-end processing machinery in RNAP II-dependent gene looping. Genes Dev 19:2969–2978PubMedGoogle Scholar
  10. Bentley DL (2005) Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors. Curr Opin Cell Biol 17:251–256PubMedGoogle Scholar
  11. Blobel G (1985) Gene gating: a hypothesis. Proc Natl Acad Sci U S A 82:8527–8529PubMedGoogle Scholar
  12. Brickner DG, Cajigas I, Fondufe-Mittendorf Y, Ahmed S, Lee PC, Widom J, Brickner JH (2007) H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS Biol 5:e81PubMedGoogle Scholar
  13. Brown CR, Silver PA (2007) Transcriptional regulation at the nuclear pore complex. Curr Opin Genet Dev 17:100–106PubMedGoogle Scholar
  14. Buratowski S (2005) Connections between mRNA 3′ end processing and transcription termination. Curr Opin Cell Biol 17:257–261PubMedGoogle Scholar
  15. Cabal GG, Genovesio A, Rodriguez-Navarro S, Zimmer C, Gadal O, Lesne A, Buc H, Feuerbach-Fournier F, Olivo-Marin JC, Hurt EC, Nehrbass U (2006) SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope. Nature 441:770–773PubMedGoogle Scholar
  16. Calvo O, Manley JL (2005) The transcriptional coactivator PC4/Sub1 has multiple functions in RNA polymerase II transcription. EMBO J 24:1009–1020PubMedGoogle Scholar
  17. Casolari JM, Brown CR, Komili S, West J, Hieronymus H, Silver PA (2004) Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization. Cell 117:427–439PubMedGoogle Scholar
  18. Chang M, French-Cornay D, Fan HY, Klein H, Denis CL, Jaehning JA (1999) A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling. Mol Cell Biol 19:1056–1067PubMedGoogle Scholar
  19. Chapman RD, Heidemann M, Albert TK, Mailhammer R, Flatley A, Meisterernst M, Kremmer E, Eick D (2007) Transcribing RNA polymerase II is phosphorylated at CTD residue serine-7. Science 318:1780–1782PubMedGoogle Scholar
  20. Chávez S, Beilharz T, Rondón AG, Erdjument-Bromage H, Tempst P, Svejstrup JQ, Lithgow T, Aguilera A (2000) A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. EMBO J 19:5824–5834PubMedGoogle Scholar
  21. Chekanova JA, Abruzzi KC, Rosbash M, Belostotsky DA (2008) Sus1, Sac3, and Thp1 mediate post-transcriptional tethering of active genes to the nuclear rim as well as to non-nascent mRNP. RNA 14:66–77PubMedGoogle Scholar
  22. Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R (2006) Human mRNA export machinery recruited to the 5′ end of mRNA. Cell 127:1389–1400PubMedGoogle Scholar
  23. Cole CN, Scarcelli JJ (2006) Transport of messenger RNA from the nucleus to the cytoplasm. Curr Opin Cell Biol 18:299–306PubMedGoogle Scholar
  24. Cramer P, Bushnell DA, Kornberg RD (2001) Structural basis of transcription: RNA polymerase II at 2.8 Angstrom resolution. Science 292:1863–1876PubMedGoogle Scholar
  25. Custodio N, Carvalho C, Condado I, Antoniou M, Blencowe BJ, Carmo-Fonseca M (2004) In vivo recruitment of exon junction complex proteins to transcription sites in mammalian cell nuclei. RNA 10:622–633PubMedGoogle Scholar
  26. Dantonel JC, Murthy KG, Manley JL, Tora L (1997) Transcription factor TFIID recruits factor CPSF for formation of 3′ end of mRNA. Nature 389:399–402PubMedGoogle Scholar
  27. Dieppois G, Iglesias N, Stutz F (2006) Cotranscriptional recruitment to the mRNA export receptor Mex67p contributes to nuclear pore anchoring of activated genes. Mol Cell Biol 26:7858–7870PubMedGoogle Scholar
  28. Egloff S, O’Reilly D, Chapman RD, Taylor A, Tanzhaus K, Pitts L, Eick D, Murphy S (2007) Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science 318:1777–1779PubMedGoogle Scholar
  29. Fan HY, Merker RJ, Klein HL (2001) High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Mol Cell Biol 21:5459–5470PubMedGoogle Scholar
  30. Fischer T, Strasser K, Racz A, Rodriguez-Navarro S, Oppizzi M, Ihrig P, Lechner J, Hurt E (2002) The mRNA export machinery requires the novel Sac3p–Thp1p complex to dock at the nucleoplasmic entrance of the nuclear pores. EMBO J 21:5843–5852PubMedGoogle Scholar
  31. Fischer T, Rodriguez-Navarro S, Pereira G, Racz A, Schiebel E, Hurt E (2004) Yeast centrin Cdc31 is linked to the nuclear mRNA export machinery. Nat Cell Biol 6:840–848PubMedGoogle Scholar
  32. Fleckner J, Zhang M, Valcarcel J, Green MR (1997) U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev 11:1864–1872PubMedGoogle Scholar
  33. Gallardo M, Luna R, Erdjument-Bromage H, Tempst P, Aguilera A (2003) Nab2p and the Thp1p–Sac3p complex functionally interact at the interface between transcription and mRNA metabolism. J Biol Chem 278:24225–24232PubMedGoogle Scholar
  34. Galy V, Gadal O, Fromont-Racine M, Romano A, Jacquier A, Nehrbass U (2004) Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1. Cell 116:63–73PubMedGoogle Scholar
  35. Gatfield D, Le Hir H, Schmitt C, Braun IC, Kocher T, Wilm M, Izaurralde E (2001) The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Curr Biol 11:1716–1721PubMedGoogle Scholar
  36. Gilbert W, Guthrie C (2004) The Glc7p nuclear phosphatase promotes mRNA export by facilitating association of Mex67p with mRNA. Mol Cell 13:201–212PubMedGoogle Scholar
  37. Glover-Cutter K, Kim S, Espinosa J, Bentley DL (2008) RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes. Nat Struct Mol Biol 15:71–78PubMedGoogle Scholar
  38. Goodrich JA, Tjian R (1994) Transcription factors IIE and IIH and ATP hydrolysis direct promoter clearance by RNA polymerase II. Cell 77:145–156PubMedGoogle Scholar
  39. Green DM, Johnson CP, Hagan H, Corbett AH (2003) The C-terminal domain of myosin-like protein 1 (Mlp1p) is a docking site for heterogeneous nuclear ribonucleoproteins that are required for mRNA export. Proc Natl Acad Sci U S A 100:1010–1015PubMedGoogle Scholar
  40. Gruter P, Tabernero C, von Kobbe C, 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 1:649–659PubMedGoogle Scholar
  41. Guiguen A, Soutourina J, Dewez M, Tafforeau L, Dieu M, Raes M, Vandenhaute J, Werner M, Hermand D (2007) Recruitment of P-TEFb (Cdk9-Pch1) to chromatin by the cap-methyl transferase Pcm1 in fission yeast. EMBO J 26:1552–1559PubMedGoogle Scholar
  42. Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R (2005) Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res 65:3011–3016PubMedGoogle Scholar
  43. Gwizdek C, Iglesias N, Rodriguez MS, Ossareh-Nazari B, Hobeika M, Divita G, Stutz F, Dargemont C (2006) Ubiquitin-associated domain of Mex67 synchronizes recruitment of the mRNA export machinery with transcription. Proc Natl Acad Sci U S A 103:16376–16381PubMedGoogle Scholar
  44. Hampsey M, Reinberg D (2003) Tails of intrigue: phosphorylation of RNA polymerase II mediates histone methylation. Cell 113:429–432PubMedGoogle Scholar
  45. Hartzog GA, Wada T, Handa H, Winston F (1998) Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev 12:357–369PubMedGoogle Scholar
  46. He X, Khan AU, Cheng H, Pappas DL Jr, Hampsey M, Moore CL (2003) Functional interactions between the transcription and mRNA 3′ end processing machineries mediated by Ssu72 and Sub1. Genes Dev 17:1030–1042PubMedGoogle Scholar
  47. Hieb AR, Baran S, Goodrich JA, Kugel JF (2006) An 8 nt RNA triggers a rate-limiting shift of RNA polymerase II complexes into elongation. EMBO J 25:3100–3109PubMedGoogle Scholar
  48. Hieronymus H, Yu MC, Silver PA (2004) Genome-wide mRNA surveillance is coupled to mRNA export. Genes Dev 18:2652–2662PubMedGoogle Scholar
  49. Hosoda N, Kim YK, Lejeune F, Maquat LE (2005) CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol 12:893–901PubMedGoogle Scholar
  50. Huertas P, Aguilera A (2003) Cotranscriptionally formed DNA: RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell 12:711–721PubMedGoogle Scholar
  51. Huertas P, García-Rubio ML, Wellinger RE, Luna R, Aguilera A (2006) An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination. Mol Cell Biol 26:7451–7465PubMedGoogle Scholar
  52. Izaurralde E, Lewis J, McGuigan C, Jankowska M, Darzynkiewicz E, Mattaj IW (1994) A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78:657–668PubMedGoogle Scholar
  53. Jimeno S, Rondón AG, Luna R, Aguilera A (2002) The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability. EMBO J 21:3526–3535PubMedGoogle Scholar
  54. Jimeno S, Luna R, García-Rubio M, Aguilera A (2006) Tho1, a novel hnRNP, and Sub2 provide alternative pathways for mRNP biogenesis in yeast THO mutants. Mol Cell Biol 26:4387–4398PubMedGoogle Scholar
  55. Kelly SM, Pabit SA, Kitchen CM, Guo P, Marfatia KA, Murphy TJ, Corbett AH, Berland KM (2007) Recognition of polyadenosine RNA by zinc finger proteins. Proc Natl Acad Sci U S A 104:12306–12311PubMedGoogle Scholar
  56. Kim M, Ahn SH, Krogan NJ, Greenblatt JF, Buratowski S (2004a) Transitions in RNA polymerase II elongation complexes at the 3′ ends of genes. EMBO J 23:354–364PubMedGoogle Scholar
  57. Kim M, Krogan NJ, Vasiljeva L, Rando OJ, Nedea E, Greenblatt JF, Buratowski S (2004b) The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II. Nature 432:517–522PubMedGoogle Scholar
  58. Kim Guisbert K, Duncan K, Li H, Guthrie C (2005) Functional specificity of shuttling hnRNPs revealed by genome-wide analysis of their RNA binding profiles. RNA 11:383–393PubMedGoogle Scholar
  59. Kistler AL, Guthrie C (2001) Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for sub2, an essential spliceosomal ATPase. Genes Dev 15:42–49PubMedGoogle Scholar
  60. Kohler A, Hurt E (2007) Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell Biol 8:761–773PubMedGoogle Scholar
  61. Kohler A, Pascual-Garcia P, Llopis A, Zapater M, Posas F, Hurt E, Rodriguez-Navarro S (2006) The mRNA export factor Sus1 is involved in Spt/Ada/Gcn5 acetyltransferase-mediated H2B deubiquitinylation through its interaction with Ubp8 and Sgf11. Mol Biol Cell 17:4228–4236PubMedGoogle Scholar
  62. Komarnitsky P, Cho EJ, Buratowski S (2000) Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev 14:2452–2460PubMedGoogle Scholar
  63. Krishnamurthy S, He X, Reyes-Reyes M, Moore C, Hampsey M (2004) Ssu72 is an RNA polymerase II CTD phosphatase. Mol Cell 14:387–394PubMedGoogle Scholar
  64. Kurshakova MM, Krasnov AN, Kopytova DV, Shidlovskii YV, Nikolenko JV, Nabirochkina EN, Spehner D, Schultz P, Tora L, Georgieva SG (2007) SAGA and a novel Drosophila export complex anchor efficient transcription and mRNA export to NPC. EMBO J 26:4956–4965PubMedGoogle Scholar
  65. Le Hir H, Gatfield D, Izaurralde E, Moore MJ (2001) The exon–exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J 20:4987–4997PubMedGoogle Scholar
  66. Lei EP, Krebber H, Silver PA (2001) Messenger RNAs are recruited for nuclear export during transcription. Genes Dev 15:1771–1782PubMedGoogle Scholar
  67. Lei EP, Stern CA, Fahrenkrog B, Krebber H, Moy TI, Aebi U, Silver PA (2003) Sac3 is an mRNA export factor that localizes to cytoplasmic fibrils of nuclear pore complex. Mol Biol Cell 14:836–847PubMedGoogle Scholar
  68. Li X, Manley JL (2005) Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 122:365–378PubMedGoogle Scholar
  69. Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719PubMedGoogle Scholar
  70. Libri D, Graziani N, Saguez C, Boulay J (2001) Multiple roles for the yeast SUB2/yUAP56 gene in splicing. Genes Dev 15:36–41PubMedGoogle Scholar
  71. Licatalosi DD, Geiger G, Minet M, Schroeder S, Cilli K, McNeil JB, Bentley DL (2002) Functional interaction of yeast pre-mRNA 3′ end processing factors with RNA polymerase II. Mol Cell 9:1101–1111PubMedGoogle Scholar
  72. Linder P (2006) Dead-box proteins: a family affair-active and passive players in RNP-remodeling. Nucleic Acids Res 34:4168–4180PubMedGoogle Scholar
  73. Luna R, Jimeno S, Marin M, Huertas P, García-Rubio M, Aguilera A (2005) Interdependence between transcription and mRNP processing and export, and its impact on genetic stability. Mol Cell 18:711–722PubMedGoogle Scholar
  74. Luo ML, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M, Reed R (2001) Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 413:644–647PubMedGoogle Scholar
  75. Luo W, Johnson AW, Bentley DL (2006) The role of Rat1 in coupling mRNA 3′-end processing to transcription termination: implications for a unified allosteric-torpedo model. Genes Dev 20:954–965PubMedGoogle Scholar
  76. Mandal SS, Chu C, Wada T, Handa H, Shatkin AJ, Reinberg D (2004) Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase II. Proc Natl Acad Sci U S A 101:7572–7577PubMedGoogle Scholar
  77. Mason PB, Struhl K (2005) Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo. Mol Cell 17:831–840PubMedGoogle Scholar
  78. Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R (2005) Recruitment of the human TREX complex to mRNA during splicing. Genes Dev 19:1512–1517PubMedGoogle Scholar
  79. Meinhart A, Cramer P (2004) Recognition of RNA polymerase II carboxy-terminal domain by 3′-RNA-processing factors. Nature 430:223–226PubMedGoogle Scholar
  80. Mendjan S, Taipale M, Kind J, Holz H, Gebhardt P, Schelder M, Vermeulen M, Buscaino A, Duncan K, Mueller J, Wilm M, Stunnenberg HG, Saumweber H, Akhtar A (2006) Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol Cell 21:811–823PubMedGoogle Scholar
  81. Menon BB, Sarma NJ, Pasula S, Deminoff SJ, Willis KA, Barbara KE, Andrews B, Santangelo GM (2005) Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation. Proc Natl Acad Sci U S A 102:5749–5754PubMedGoogle Scholar
  82. Moore MJ, Schwartzfarb EM, Silver PA, Yu MC (2006) Differential recruitment of the splicing machinery during transcription predicts genome-wide patterns of mRNA splicing. Mol Cell 24:903–915PubMedGoogle Scholar
  83. Moteki S, Price D (2002) Functional coupling of capping and transcription of mRNA. Mol Cell 10:599–609PubMedGoogle Scholar
  84. Muse GW, Gilchrist DA, Nechaev S, Shah R, Parker JS, Grissom SF, Zeitlinger J, Adelman K (2007) RNA polymerase is poised for activation across the genome. Nat Genet 39:1507–1511PubMedGoogle Scholar
  85. Myers LC, Lacomis L, Erdjument-Bromage H, Tempst P (2002) The yeast capping enzyme represses RNA polymerase II transcription. Mol Cell 10:883–894PubMedGoogle Scholar
  86. Nedea E, He X, Kim M, Pootoolal J, Zhong G, Canadien V, Hughes T, Buratowski S, Moore CL, Greenblatt J (2003) Organization and function of APT, a subcomplex of the yeast cleavage and polyadenylation factor involved in the formation of mRNA and small nucleolar RNA 3′-ends. J Biol Chem 278:33000–33010PubMedGoogle Scholar
  87. O’Sullivan JM, Tan-Wong SM, Morillon A, Lee B, Coles J, Mellor J, Proudfoot NJ (2004) Gene loops juxtapose promoters and terminators in yeast. Nat Genet 36:1014–1018PubMedGoogle Scholar
  88. Pei Y, Schwer B, Shuman S (2003) Interactions between fission yeast Cdk9, its cyclin partner Pch1, and mRNA capping enzyme Pct1 suggest an elongation checkpoint for mRNA quality control. J Biol Chem 278:7180–7188PubMedGoogle Scholar
  89. Peterlin BM, Price DH (2006) Controlling the elongation phase of transcription with P-TEFb. Mol Cell 23:297–305PubMedGoogle Scholar
  90. Phatnani HP, Greenleaf AL (2006) Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev 20:2922–2936PubMedGoogle Scholar
  91. Pokholok DK, Hannett NM, Young RA (2002) Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9:799–809PubMedGoogle Scholar
  92. Ragoczy T, Bender MA, Telling A, Byron R, Groudine M (2006) The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev 20:1447–1457PubMedGoogle Scholar
  93. Rasmussen EB, Lis JT (1993) In vivo transcriptional pausing and cap formation on three Drosophila heat shock genes. Proc Natl Acad Sci U S A 90:7923–7927PubMedGoogle Scholar
  94. Rehwinkel J, Herold A, Gari K, Kocher T, Rode M, Ciccarelli FL, Wilm M, Izaurralde E (2004) Genome-wide analysis of mRNAs regulated by the THO complex in Drosophila melanogaster. Nat Struct Mol Biol 11:558–566PubMedGoogle Scholar
  95. Reinberg D, Sims RJ 3rd (2006) de FACTo nucleosome dynamics. J Biol Chem 281:23297–23301PubMedGoogle Scholar
  96. Rodriguez MS, Dargemont C, Stutz F (2004) Nuclear export of RNA. Biol Cell 96:639–655PubMedGoogle Scholar
  97. Rodriguez-Navarro S, Fischer T, Luo MJ, Antunez O, Brettschneider S, Lechner J, Perez-Ortin JE, Reed R, Hurt E (2004) Sus1, a functional component of the SAGA histone acetylase complex and the nuclear pore-associated mRNA export machinery. Cell 116:75–86PubMedGoogle Scholar
  98. Rondón AG, García-Rubio M, Gonzalez-Barrera S, Aguilera A (2003a) Molecular evidence for a positive role of Spt4 in transcription elongation. EMBO J 22:612–620PubMedGoogle Scholar
  99. Rondón AG, Jimeno S, García-Rubio M, Aguilera A (2003b) Molecular evidence that the eukaryotic THO/TREX complex is required for efficient transcription elongation. J Biol Chem 278:39037–39043PubMedGoogle Scholar
  100. Rosonina E, Kaneko S, Manley JL (2006) Terminating the transcript: breaking up is hard to do. Genes Dev 20:1050–1056PubMedGoogle Scholar
  101. Saguez C, Olesen JR, Jensen TH (2005) Formation of export-competent mRNP: escaping nuclear destruction. Curr Opin Cell Biol 17:287–293PubMedGoogle Scholar
  102. Saunders A, Core LJ, Lis JT (2006) Breaking barriers to transcription elongation. Nat Rev Mol Cell Biol 7:557–567PubMedGoogle Scholar
  103. Schmid M, Arib G, Laemmli C, Nishikawa J, Durussel T, Laemmli UK (2006) Nup-PI: the nucleopore-promoter interaction of genes in yeast. Mol Cell 21:379–391PubMedGoogle Scholar
  104. Schneider R, Grosschedl R (2007) Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev 21:3027–3043PubMedGoogle Scholar
  105. Schroeder SC, Schwer B, Shuman S, Bentley D (2000) Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev 14:2435–2440PubMedGoogle Scholar
  106. Schroeder SC, Zorio DA, Schwer B, Shuman S, Bentley D (2004) A function of yeast mRNA cap methyltransferase, Abd1, in transcription by RNA polymerase II. Mol Cell 13:377–387PubMedGoogle Scholar
  107. 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 16:3256–3271PubMedGoogle Scholar
  108. Shi H, Cordin O, Minder CM, Linder P, Xu RM (2004) Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A 101:17628–17633PubMedGoogle Scholar
  109. Shilatifard A (2006) Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75:243–269PubMedGoogle Scholar
  110. Sims RJ 3rd, Belotserkovskaya R, Reinberg D (2004a) Elongation by RNA polymerase II: the short and long of it. Genes Dev 18:2437–2468PubMedGoogle Scholar
  111. Sims RJ 3rd, Mandal SS, Reinberg D (2004b) Recent highlights of RNA-polymerase-II-mediated transcription. Curr Opin Cell Biol 16:263–271PubMedGoogle Scholar
  112. Singh BN, Hampsey M (2007) A transcription-independent role for TFIIB in gene looping. Mol Cell 27:806–816PubMedGoogle Scholar
  113. Sommer P, Nehrbass U (2005) Quality control of messenger ribonucleoprotein particles in the nucleus and at the pore. Curr Opin Cell Biol 17:294–301PubMedGoogle Scholar
  114. Spector DL (2003) The dynamics of chromosome organization and gene regulation. Annu Rev Biochem 72:573–608PubMedGoogle Scholar
  115. Steinmetz EJ, Brow DA (2003) Ssu72 protein mediates both poly(A)-coupled and poly(A)-independent termination of RNA polymerase II transcription. Mol Cell Biol 23:6339–6349PubMedGoogle Scholar
  116. Strasser K, Hurt E (2001) Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p. Nature 413:648–652PubMedGoogle Scholar
  117. Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondón AG, Aguilera A, Struhl K, Reed R, Hurt E (2002) TREX is a conserved complex coupling transcription with messenger RNA export. Nature 417:304–308PubMedGoogle Scholar
  118. Stutz F, Bachi A, Doerks T, Braun IC, Seraphin B, Wilm M, Bork P, Izaurralde E (2000) REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA 6:638–650PubMedGoogle Scholar
  119. Svejstrup JQ (2007) Elongator complex: how many roles does it play? Curr Opin Cell Biol 19:331–336PubMedGoogle Scholar
  120. Taddei A, Van Houwe G, Hediger F, Kalck V, Cubizolles F, Schober H, Gasser SM (2006) Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441:774–778PubMedGoogle Scholar
  121. Tran EJ, Zhou Y, Corbett AH, Wente SR (2007) The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein remodeling events. Mol Cell 28:850–859PubMedGoogle Scholar
  122. Vinciguerra P, Iglesias N, Camblong J, Zenklusen D, Stutz F (2005) Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export. EMBO J 24:813–823PubMedGoogle Scholar
  123. Voynov V, Verstrepen KJ, Jansen A, Runner VM, Buratowski S, Fink GR (2006) Genes with internal repeats require the THO complex for transcription. Proc Natl Acad Sci U S A 103:14423–14428PubMedGoogle Scholar
  124. Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, Sugimoto S, Yano K, Hartzog GA, Winston F, Buratowski S, Handa H (1998) DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev 12:343–356PubMedGoogle Scholar
  125. Wellinger RE, Prado F, Aguilera A (2006) Replication fork progression is impaired by transcription in hyperrecombinant yeast cells lacking a functional THO complex. Mol Cell Biol 26:3327–3334PubMedGoogle Scholar
  126. West S, Gromak N, Proudfoot NJ (2004) Human 5′→ 3′ exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. Nature 432:522–525PubMedGoogle Scholar
  127. Wong CM, Qiu H, Hu C, Dong J, Hinnebusch AG (2007) Yeast cap binding complex impedes recruitment of cleavage factor IA to weak termination sites. Mol Cell Biol 27:6520–6531PubMedGoogle Scholar
  128. Wood A, Shilatifard A (2006) Bur1/Bur2 and the Ctk complex in yeast: the split personality of mammalian P-TEFb. Cell Cycle 5:1066–1068PubMedGoogle Scholar
  129. Wu CH, Yamaguchi Y, Benjamin LR, Horvat-Gordon M, Washinsky J, Enerly E, Larsson J, Lambertsson A, Handa H, Gilmour D (2003) NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila. Genes Dev 17:1402–1414PubMedGoogle Scholar
  130. Yamada T, Yamaguchi Y, Inukai N, Okamoto S, Mura T, Handa H (2006) P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation. Mol Cell 21:227–237PubMedGoogle Scholar
  131. Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H (1999) NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97:41–51PubMedGoogle Scholar
  132. Yoh SM, Cho H, Pickle L, Evans RM, Jones KA (2007) The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export. Genes Dev 21:160–174PubMedGoogle Scholar
  133. Zeitlinger J, Stark A, Kellis M, Hong JW, Nechaev S, Adelman K, Levine M, Young RA (2007) RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat Genet 39:1512–1516PubMedGoogle Scholar
  134. Zenklusen D, Vinciguerra P, Wyss JC, Stutz F (2002) Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p. Mol Cell Biol 22:8241–8253PubMedGoogle Scholar
  135. Zhang Z, Gilmour DS (2006) 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 21:65–74PubMedGoogle Scholar
  136. Zhang Z, Fu J, Gilmour DS (2005) CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3′-end processing factor, Pcf11. Genes Dev 19:1572–1580PubMedGoogle Scholar
  137. Zhao Y, Lang G, Ito S, Bonnet J, Metzger E, Sawatsubashi S, Suzuki E, Le Guezennec X, Stunnenberg HG, Krasnov A, Georgieva SG, Schule R, Takeyama K, Kato S, Tora L, Devys D (2008) A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Mol Cell 29:92–101PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Rosa Luna
    • 1
  • Hélène Gaillard
    • 1
  • Cristina González-Aguilera
    • 1
  • Andrés Aguilera
    • 1
    Email author
  1. 1.Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)SevilleSpain

Personalised recommendations