title: Kaposi's sarcoma-associated herpesvirus ORF57 protein: exploiting all stages of viral mRNA processing.
abstract: Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi's sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms.
authors.affiliation: School of Molecular and Cellular Biology, and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Schumann
authors.forename: Brian R
authors.initials: BR
authors.lastname: Jackson
authors.forename: Belinda
authors.initials: B
authors.lastname: Baquero-Perez
authors.forename: Adrian
authors.initials: A
authors.lastname: Whitehouse
mesh_terms: D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins
references.citation: J Virol. 2006 Jun;80(11):5251-60
references.pmid: 16699005
references.citation: Cell Rep. 2013 Apr 25;3(4):988-95
references.pmid: 23583177
references.citation: J Virol. 2011 Mar;85(6):2620-30
references.pmid: 21209110
references.citation: Nat Struct Biol. 2000 Oct;7(10):838-42
references.pmid: 11017188
references.citation: Cell. 2006 Dec 29;127(7):1389-400
references.pmid: 17190602
references.citation: Front Microbiol. 2012 Feb 20;3:59
references.pmid: 22363332
references.citation: J Biol Chem. 2006 Apr 21;281(16):10912-25
references.pmid: 16484227
references.citation: PLoS One. 2009 Nov 18;4(11):e7882
references.pmid: 19924249
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):761-73
references.pmid: 17786152
references.citation: Mol Cell Biol. 2002 Dec;22(23):8254-66
references.pmid: 12417728
references.citation: Cell. 1991 Apr 19;65(2):241-8
references.pmid: 2015625
references.citation: RNA Biol. 2009 Jul-Aug;6(3):237-41
references.pmid: 19574733
references.citation: J Biol Chem. 2001 Jun 8;276(23):19905-12
references.pmid: 11278515
references.citation: J Virol. 1997 Jan;71(1):715-9
references.pmid: 8985403
references.citation: Lancet Oncol. 2008 Aug;9(8):786-95
references.pmid: 18672214
references.citation: Cell. 2012 May 11;149(4):832-46
references.pmid: 22579286
references.citation: J Cell Sci. 2003 Feb 15;116(Pt 4):587-97
references.pmid: 12538759
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5154-9
references.pmid: 18364396
references.citation: J Virol. 1998 Aug;72(8):6602-7
references.pmid: 9658105
references.citation: J Virol. 1998 Dec;72(12):9526-34
references.pmid: 9811685
references.citation: Curr Opin Cell Biol. 2005 Jun;17(3):242-50
references.pmid: 15901492
references.citation: Genes Dev. 2002 Nov 1;16(21):2761-6
references.pmid: 12414728
references.citation: PLoS Pathog. 2011 Jan 06;7(1):e1001244
references.pmid: 21253573
references.citation: Lancet Oncol. 2008 Jul;9(7):683-92
references.pmid: 18598933
references.citation: J Clin Invest. 2011 Mar;121(3):1130-40
references.pmid: 21339648
references.citation: J Virol. 2009 Jul;83(13):6335-46
references.pmid: 19369354
references.citation: Blood. 1995 Aug 15;86(4):1276-80
references.pmid: 7632932
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15190-5
references.pmid: 17005724
references.citation: Nucleic Acids Res. 2013 Aug;41(14):7060-72
references.pmid: 23685434
references.citation: Virology. 2011 Oct 25;419(2):107-16
references.pmid: 21889182
references.citation: EMBO J. 2013 Feb 6;32(3):473-86
references.pmid: 23299939
references.citation: J Biol Chem. 2003 Jan 3;278(1):335-42
references.pmid: 12403791
references.citation: J Biol Chem. 2006 Sep 22;281(38):28365-78
references.pmid: 16829516
references.citation: Genes Dev. 2004 Jan 15;18(2):210-22
references.pmid: 14752011
references.citation: PLoS One. 2012;7(8):e43804
references.pmid: 22928037
references.citation: RNA. 2006 Nov;12(11):1933-48
references.pmid: 17000901
references.citation: Cell Cycle. 2010 Jul 15;9(14):2702-3
references.pmid: 20686356
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60
references.pmid: 8108397
references.citation: Curr Biol. 2009 Dec 1;19(22):1918-24
references.pmid: 19836239
references.citation: Nat Commun. 2012;3:1006
references.pmid: 22893130
references.citation: Front Microbiol. 2012 May 18;3:179
references.pmid: 22783232
references.citation: Mol Cell Biol. 2006 Mar;26(5):1631-43
references.pmid: 16478985
references.citation: J Gen Virol. 2000 Sep;81(Pt 9):2253-2265
references.pmid: 10950983
references.citation: Front Biosci. 2008 Jan 01;13:2939-49
references.pmid: 17981767
references.citation: Cell. 2002 Feb 22;108(4):523-31
references.pmid: 11909523
references.citation: Genes Dev. 2010 Sep 15;24(18):2043-53
references.pmid: 20844015
references.citation: Annu Rev Pathol. 2006;1:273-96
references.pmid: 18039116
references.citation: J Biol Chem. 1997 Nov 21;272(47):29742-51
references.pmid: 9368044
references.citation: Trends Cell Biol. 2003 Jun;13(6):319-27
references.pmid: 12791298
references.citation: J Virol. 2004 Apr;78(8):4074-84
references.pmid: 15047824
references.citation: Cell. 1995 Aug 11;82(3):475-83
references.pmid: 7543368
references.citation: Mol Biol Cell. 2010 Aug 15;21(16):2953-65
references.pmid: 20573985
references.citation: Blood. 2001 May 15;97(10):3244-50
references.pmid: 11342455
references.citation: Nat Rev Mol Cell Biol. 2002 Aug;3(8):575-85
references.pmid: 12154369
references.citation: Nucleic Acids Res. 2010 Jun;38(10):3351-61
references.pmid: 20129943
references.citation: Nature. 1993 Oct 14;365(6447):661-3
references.pmid: 8413630
references.citation: Biochem J. 2005 Apr 15;387(Pt 2):295-308
references.pmid: 15537388
references.citation: EMBO J. 2009 Mar 4;28(5):556-67
references.pmid: 19165146
references.citation: Front Biosci. 2008 May 01;13:5241-56
references.pmid: 18508584
references.citation: J Virol. 2013 Jan;87(1):243-56
references.pmid: 23077296
references.citation: Annu Rev Biochem. 2007;76:51-74
references.pmid: 17352659
references.citation: Nucleic Acids Res. 2012 Feb;40(3):1226-39
references.pmid: 21993300
references.citation: Nat Struct Mol Biol. 2004 Jun;11(6):558-66
references.pmid: 15133499
references.citation: J Gen Virol. 2010 May;91(Pt 5):1290-301
references.pmid: 20071484
references.citation: Semin Cell Dev Biol. 2007 Apr;18(2):186-93
references.pmid: 17459736
references.citation: EMBO J. 2010 Jun 2;29(11):1851-64
references.pmid: 20436455
references.citation: EMBO J. 2000 Dec 15;19(24):6860-9
references.pmid: 11118221
references.citation: Science. 1995 Apr 28;268(5210):582-3
references.pmid: 7725108
references.citation: N Engl J Med. 1995 May 4;332(18):1186-91
references.pmid: 7700311
references.citation: Annu Rev Cell Dev Biol. 1999;15:607-60
references.pmid: 10611974
references.citation: Cancer Detect Prev. 1988;12(1-6):39-57
references.pmid: 3052837
references.citation: J Virol. 2007 Dec;81(24):13299-314
references.pmid: 17913801
references.citation: J Gen Virol. 2009 Jun;90(Pt 6):1455-1460
references.pmid: 19264631
references.citation: J Clin Invest. 2010 Apr;120(4):939-49
references.pmid: 20364091
references.citation: Cell. 1997 Sep 19;90(6):1051-60
references.pmid: 9323133
references.citation: Nature. 2001 Oct 4;413(6855):538-42
references.pmid: 11586364
references.citation: Mol Cell. 1998 Apr;1(5):649-59
references.pmid: 9660949
references.citation: Mol Cell Biol. 2008 Jan;28(2):601-8
references.pmid: 17984224
references.citation: Nature. 2002 May 16;417(6886):304-8
references.pmid: 11979277
references.citation: Nature. 2001 Oct 11;413(6856):644-7
references.pmid: 11675789
references.citation: Genes Dev. 2005 Jul 1;19(13):1512-7
references.pmid: 15998806
references.citation: Front Microbiol. 2012 Sep 06;3:330
references.pmid: 22973269
references.citation: Front Biosci. 2008 Jan 01;13:2928-38
references.pmid: 17981766
references.citation: Trends Biochem Sci. 2003 Aug;28(8):419-24
references.pmid: 12932730
references.citation: Mol Cell. 2007 Feb 9;25(3):327-30
references.pmid: 17289581
references.citation: J Gen Virol. 1999 Dec;80 ( Pt 12):3207-3215
references.pmid: 10567653
references.citation: PLoS Pathog. 2008 Oct;4(10):e1000194
references.pmid: 18974867
references.citation: J Virol. 2004 Jan;78(1):340-52
references.pmid: 14671116
references.citation: J Virol. 2009 Jul;83(13):6727-38
references.pmid: 19369342
references.citation: Mol Cell. 2003 Mar;11(3):837-43
references.pmid: 12667464
references.citation: J Cell Biol. 2000 Oct 2;151(1):1-14
references.pmid: 11018049
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):17985-90
references.pmid: 22010220
references.citation: J Virol. 2011 Feb;85(4):1528-40
references.pmid: 21106733
references.citation: Nucleic Acids Res. 2013 Jan;41(2):1294-306
references.pmid: 23222130
references.citation: J Virol. 2013 Jul;87(13):7210-7
references.pmid: 23637401
references.citation: FEBS Lett. 2009 Nov 19;583(22):3549-56
references.pmid: 19850040
references.citation: J Gen Virol. 2004 Aug;85(Pt 8):2155-2166
references.pmid: 15269354
references.citation: J Biol Chem. 2004 Jul 30;279(31):33001-11
references.pmid: 15155762
references.citation: J Virol. 2000 Apr;74(8):3586-97
references.pmid: 10729134
references.citation: PLoS Pathog. 2011 Jul;7(7):e1002138
references.pmid: 21814512
references.citation: Adv Dent Res. 2006 Apr 01;19(1):91-5
references.pmid: 16672557
references.citation: J Virol. 2008 Mar;82(6):2792-801
references.pmid: 18184716
references.citation: RNA. 2000 Dec;6(12):1737-49
references.pmid: 11142374
references.citation: Cell. 2008 Apr 18;133(2):303-13
references.pmid: 18423201
references.citation: Nucleic Acids Res. 2013 Feb 1;41(4):2517-25
references.pmid: 23275560
references.citation: J Cell Biol. 2009 Jan 12;184(1):31-44
references.pmid: 19124654
references.citation: Mol Cell Biol. 2002 Dec;22(23):8241-53
references.pmid: 12417727
references.citation: Nat Struct Mol Biol. 2007 Dec;14(12):1173-9
references.pmid: 18026120
references.citation: J Virol. 2007 Sep;81(18):9990-8
references.pmid: 17609285
references.citation: Nat Struct Mol Biol. 2011 Sep 25;18(10):1164-71
references.pmid: 21947206
references.citation: Rev Med Virol. 2010 Jul;20(4):214-30
references.pmid: 20069615
references.citation: Nature. 2000 Sep 21;407(6802):401-5
references.pmid: 11014198
references.citation: J Virol. 2013 Apr;87(7):4005-16
references.pmid: 23365430
references.citation: Microbiol Mol Biol Rev. 2003 Jun;67(2):175-212, table of contents
references.pmid: 12794189
references.citation: J Virol. 2008 Jul;82(14):7180-8
references.pmid: 18463151
references.citation: J Virol. 2011 Aug;85(15):7881-91
references.pmid: 21593148
references.citation: J Virol. 2012 Sep;86(18):9866-74
references.pmid: 22761374
references.citation: Nat Rev Cancer. 2010 Oct;10(10):707-19
references.pmid: 20865011
references.citation: Curr Opin Cell Biol. 2005 Jun;17(3):269-73
references.pmid: 15901496
references.citation: PLoS Pathog. 2010 Mar 05;6(3):e1000799
references.pmid: 20221435
references.citation: Nucleic Acids Res. 2012 Feb;40(3):1214-25
references.pmid: 21993299
references.citation: Mol Cell. 2011 Sep 16;43(6):853-66
references.pmid: 21925375
references.citation: Mol Cell Biol. 2012 Apr;32(7):1260-70
references.pmid: 22290432
references.citation: EMBO J. 2002 Jul 1;21(13):3536-45
references.pmid: 12093754
references.citation: J Biol Chem. 1998 Sep 4;273(36):22857-60
references.pmid: 9722501
references.citation: J Virol. 1996 Jan;70(1):549-58
references.pmid: 8523568
references.citation: Science. 1994 Dec 16;266(5192):1865-9
references.pmid: 7997879
references.citation: Mol Cell. 2009 Jan 30;33(2):215-26
references.pmid: 19110458
references.citation: Genes Dev. 2000 Dec 15;14(24):3102-14
references.pmid: 11124803
references.citation: Nature. 1989 Mar 16;338(6212):254-7
references.pmid: 2784194
references.citation: Biochem Soc Trans. 2006 Nov;34(Pt 5):705-10
references.pmid: 17052179
references.citation: Int J Biol Sci. 2011;7(8):1145-60
references.pmid: 22043172
references.citation: Genes Dev. 1998 Mar 15;12(6):868-79
references.pmid: 9512520