The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs.
Vyšlo v časopise: An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export. PLoS Pathog 7(7): e32767. doi:10.1371/journal.ppat.1002138 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002138
1. MooreMJ 2005 From birth to death: the complex lives of eukaryotic mRNAs. Science 309 1514 1518
2. BentleyDL 2005 Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors. Curr Opin Cell Biol 17 251 256
3. KohlerAHurtE 2007 Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell Biol 8 761 773
4. MooreMJProudfootNJ 2009 Pre-mRNA processing reaches back to transcription and ahead to translation. Cell 136 688 700
5. ReedRChengH 2005 TREX, SR proteins and export of mRNA. Curr Opin Cell Biol 17 269 273
6. ChengHDufuKLeeCSHsuJLDiasA 2006 Human mRNA export machinery recruited to the 5′ end of mRNA. Cell 127 1389 1400
7. MasudaSDasRChengHHurtEDormanN 2005 Recruitment of the human TREX complex to mRNA during splicing. Genes Dev 19 1512 1517
8. Le HirHIzaurraldeEMaquatLEMooreMJ 2000 The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon-exon junctions. EMBO J 19 6860 6869
9. ChangYFImamJSWilkinsonMF 2007 The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76 51 74
10. DiemMDChanCCYounisIDreyfussG 2007 PYM binds the cytoplasmic exon-junction complex and ribosomes to enhance translation of spliced mRNAs. Nat Struct Mol Biol 14 1173 1179
11. MaXMYoonSORichardsonCJJulichKBlenisJ 2008 SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell 133 303 313
12. NottALe HirHMooreMJ 2004 Splicing enhances translation in mammalian cells: an additional function of the exon junction complex. Genes Dev 18 210 222
13. ReedRHurtE 2002 A conserved mRNA export machinery coupled to pre-mRNA splicing. Cell 108 523 531
14. StrasserKMasudaSMasonPPfannstielJOppizziM 2002 TREX is a conserved complex coupling transcription with messenger RNA export. Nature 417 304 308
15. DufuKLivingstoneMJSeebacherJGygiSPWilsonSA 2010 ATP is required for interactions between UAP56 and two conserved mRNA export proteins, Aly and CIP29, to assemble the TREX complex. Genes Dev 24 2043 2053
16. LuoMJReedR 1999 Splicing is required for rapid and efficient mRNA export in metazoans. Proc Natl Acad Sci U S A 96 14937 14942
17. ValenciaPDiasAPReedR 2008 Splicing promotes rapid and efficient mRNA export in mammalian cells. Proc Natl Acad Sci U S A 105 3386 3391
18. ZhouZLuoMJStraesserKKatahiraJHurtE 2000 The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans. Nature 407 401 405
19. KatahiraJStrasserKPodtelejnikovAMannMJungJU 1999 The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J 18 2593 2609
20. StutzFBachiADoerksTBraunICSeraphinB 2000 REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA 6 638 650
21. HautbergueGMHungMLGolovanovAPLianLYWilsonSA 2008 Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP. Proc Natl Acad Sci U S A 105 5154 5159
22. FribourgSBraunICIzaurraldeEContiE 2001 Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. Mol Cell 8 645 656
23. GatfieldDIzaurraldeE 2002 REF1/Aly and the additional exon junction complex proteins are dispensable for nuclear mRNA export. J Cell Biol 159 579 588
24. LongmanDJohnstoneILCaceresJF 2003 The Ref/Aly proteins are dispensable for mRNA export and development in Caenorhabditis elegans. RNA 9 881 891
25. HeroldAKlymenkoTIzaurraldeE 2001 NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila. RNA 7 1768 1780
26. RehwinkelJHeroldAGariKKocherTRodeM 2004 Genome-wide analysis of mRNAs regulated by the THO complex in Drosophila melanogaster. Nat Struct Mol Biol 11 558 566
27. FarnyNGHurtJASilverPA 2008 Definition of global and transcript-specific mRNA export pathways in metazoans. Genes Dev 22 66 78
28. HautbergueGMHungMLWalshMJSnijdersAPChangCT 2009 UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA. Curr Biol 19 1918 1924
29. BoyneJRWhitehouseA 2006 gamma-2 Herpes virus post-transcriptional gene regulation. Clin Microbiol Infect 12 110 117
30. BoyneJRJacksonBRWhitehouseA 2010 ORF57: Master regulator of KSHV mRNA biogenesis. Cell Cycle 9 2702 2703
31. ChangYMoorePS 1996 Kaposi's sarcoma (KS)-associated herpesvirus and its role in KS. Infect Agents Dis 5 215 222
32. BoshoffCChangY 2001 Kaposi's sarcoma - Associated herpesvirus: A new DNA tumor virus. Ann Rev Med 52 453 470
33. GanemD 2006 KSHV infection and the pathogenesis of Kaposi's sarcoma. Annu Rev Pathol 1 273 296
34. MajerciakVZhengZM 2009 Kaposi's sarcoma-associated herpesvirus ORF57 in viral RNA processing. Front Biosci 14 1516 1528
35. SwaminathanS 2005 Post-transcriptional gene regulation by gamma herpesviruses. J Cell Biochem 95 698 711
36. BoyneJRJacksonBTaylorAMacnabSWhitehouseA 2010 KSHV ORF57 interacts with PYM to enhance the translation of viral intronless mRNAs. EMBO J 29 1851 1864
37. BoyneJRColganKJWhitehouseA 2008 Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog 4 e1000194
38. MajerciakVYamanegiKAllemandEKruhlakMKrainerAR 2008 Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing. J Virol 82 2792 2801
39. SahinBBPatelDConradNK 2010 Kaposi's sarcoma-associated herpesvirus ORF57 protein binds and protects a nuclear noncoding RNA from cellular RNA decay pathways. PLoS Pathog 6 e1000799
40. ColganKJBoyneJRWhitehouseA 2009 Uncoupling of hTREX demonstrates that UAP56 and hTHO-complex recruitment onto herpesvirus saimiri intronless transcripts is required for replication. J Gen Virol 90 1455 1460
41. BoyneJRColganKJWhitehouseA 2008 Herpesvirus saimiri ORF57: a post-transcriptional regulatory protein. Front Biosci 13 2928 2938
42. MajerciakVYamanegiKNieSHZhengZM 2006 Structural and functional analyses of Kaposi sarcoma-associated herpesvirus ORF57 nuclear localization signals in living cells. J Biol Chem 281 28365 28378
43. KoffaMDClementsJBIzaurraldeEWaddSWilsonSA 2001 Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway. EMBO J 20 5769 5778
44. JohnsonLALiLSandri-GoldinRM 2009 The cellular RNA export receptor TAP/NXF1 is required for ICP27-mediated export of herpes simplex virus 1 RNA, but the TREX complex adaptor protein Aly/REF appears to be dispensable. J Virol 83 6335 6346
45. Escudero-PaunettoLLiLHernandezFPSandri-GoldinRM 2010 SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs. Virology 401 155 164
46. BoyneJRWhitehouseA 2009 Nucleolar disruption impairs Kaposi's sarcoma-associated herpesvirus ORF57-mediated nuclear export of intronless viral mRNAs. FEBS Letters 583 3549 3556
47. LuoMLZhouZMagniKChristoforidesCRappsilberJ 2001 Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 413 644 647
48. GriffithsRWhitehouseA 2007 Herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein MeCP2. J Virol 81 4021 4032
49. MajerciakVDengMZhengZM 2010 Requirement of UAP56, URH49, RBM15, and OTT3 in the expression of Kaposi sarcoma-associated herpesvirus ORF57. Virology 407 206 212
50. KatahiraJInoueHHurtEYonedaY 2009 Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. EMBO J 28 556 567
51. YamazakiTFujiwaraNYukinagaHEbisuyaMShikiT 2010 The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression. Mol Biol Cell 21 2953 2965
52. UranishiHZolotukhinASLindtnerSWarmingSZhangGM 2009 The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1. J Biol Chem 284 26106 26116
53. ChenIHLiLSilvaLSandri-GoldinRM 2005 ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 export. J Virol 79 3949 3961
54. VermaDBaisSGaillardMSwaminathanS 2010 Epstein-Barr Virus SM protein utilizes cellular splicing factor SRp20 to mediate alternative splicing. J Virol 84 11781 11789
55. BoyleSMRuvoloVGuptaAKSwaminathanS 1999 Association with the cellular export receptor CRM 1 mediates function and intracellular localization of Epstein-Barr virus SM protein, a regulator of gene expression. J Virol 73 6872 6881
56. LischkaPTothZThomasMMuellerRStammingerT 2006 The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA. Mol Cell Biol 26 1631 1643
57. HaoLSakuraiAWatanabeTSorensenENidomCA 2008 Drosophila RNAi screen identifies host genes important for influenza virus replication. Nature 454 890 893
58. ReadEKDigardP 2010 Individual influenza A virus mRNAs show differential dependence on cellular NXF1/TAP for their nuclear export. J Gen Virol 91 1290 1301
59. TunnicliffeRBHautbergueGMKalraPJacksonBRWhitehouseA 2011 Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57. PLoS Pathog 7 e1001244
60. VieiraJO'HearnPM 2004 Use of the red fluorescent protein as a marker of Kaposi's sarcoma-associated herpesvirus lytic gene expression. Virology 325 225 240
61. CalderwoodMAHallKTMatthewsDAWhitehouseA 2004 The herpesvirus saimiri ORF73 gene product interacts with host-cell mitotic chromosomes and self-associates via its C terminus. J Gen Virol 85 147 153
62. GouldFHarrisonSMHewittEWWhitehouseA 2009 Kaposi's sarcoma-associated herpesvirus RTA promotes degradation of the Hey1 repressor protein through the ubiquitin proteasome pathway. J Virol 83 6727 6738
63. HallKTGilesMSCalderwoodMAGoodwinDJMatthewsDA 2002 The herpesvirus saimiri open reading frame 73 gene product interacts with the cellular protein p32. J Virol 76 11612 11622
64. BoyneJRWhitehouseA 2006 Nucleolar trafficking is essential for nuclear export of intronless herpesvirus mRNA. Proc Natl Acad Sci U S A 103 15190 15195
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