title: The 5' and 3' ends of alphavirus RNAs--Non-coding is not non-functional.
abstract: The non-coding regions found at the 5' and 3' ends of alphavirus genomes regulate viral gene expression, replication, translation and virus-host interactions, which have significant implications for viral evolution, host range, and pathogenesis. The functions of these non-coding regions are mediated by a combination of linear sequence and structural elements. The capped 5' untranslated region (UTR) contains promoter elements, translational regulatory sequences that modulate dependence on cellular translation factors, and structures that help to avoid innate immune defenses. The polyadenylated 3' UTR contains highly conserved sequence elements for viral replication, binding sites for cellular miRNAs that determine cell tropism, host range, and pathogenesis, and conserved binding regions for a cellular protein that influences viral RNA stability. Nonetheless, there are additional conserved elements in non-coding regions of the virus (e.g., the repeated sequence elements in the 3' UTR) whose function remains obscure. Thus, key questions remain as to the function of these short yet influential untranslated segments of alphavirus RNAs.
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Jennifer L
authors: JL
authors: Hyde
authors: Institute for Human Infections and Immunity, Center for Tropical Diseases, and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors: Rubing
authors: R
authors: Chen
authors: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, 8031 BST3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
authors: Derek W
authors: DW
authors: Trobaugh
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diamond@wusm.wustl.edu.
authors: Michael S
authors: MS
authors: Diamond
authors: Institute for Human Infections and Immunity, Center for Tropical Diseases, and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: sweaver@utmb.edu.
authors: Scott C
authors: SC
authors: Weaver
authors: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, 8031 BST3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA. Electronic address: klimistra@pitt.edu.
authors: William B
authors: WB
authors: Klimstra
authors: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: jeffrey.wilusz@colostate.edu.
authors: Jeffrey
authors: J
authors: Wilusz
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000524:Alphavirus / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D011485:Protein Binding; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins
keywords: Polyadenylation; Protein–RNA interactions; Translation regulation; Viral pathogenesis; mRNA capping; miRNAs
references: Cell. 2013 Apr 25;153(3):654-65
references: 23622248
references: Virology. 1989 Jun;170(2):385-91
references: 2728344
references: J Virol. 2008 Jan;82(2):880-92
references: 17977976
references: Nature. 2014 Feb 13;506(7487):245-8
references: 24352241
references: J Virol. 1996 Feb;70(2):1173-81
references: 8551578
references: Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11
references: 7831320
references: Cell. 2007 Jun 29;129(7):1401-14
references: 17604727
references: Cell Rep. 2013 Nov 27;5(4):909-17
references: 24210824
references: Nature. 2014 Jan 30;505(7485):701-5
references: 24336214
references: Mol Cell Biol. 1998 Dec;18(12):7565-74
references: 9819442
references: Virology. 2008 Jan 5;370(1):158-72
references: 17900652
references: J Virol. 2000 Oct;74(20):9776-85
references: 11000254
references: Science. 2014 Feb 14;343(6172):783-7
references: 24482115
references: Cell Host Microbe. 2010 Aug 19;8(2):196-207
references: 20709296
references: J Virol. 2004 Jan;78(1):61-75
references: 14671088
references: J Virol. 2007 Mar;81(5):2472-84
references: 17108023
references: Microbiol Rev. 1994 Sep;58(3):491-562
references: 7968923
references: Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):941-6
references: 22215596
references: Nat Immunol. 2011 Feb;12(2):137-43
references: 21217758
references: Virology. 1998 Jan 5;240(1):100-8
references: 9448694
references: RNA Biol. 2010 May-Jun;7(3):291-5
references: 20400847
references: J Virol. 2001 May;75(9):4103-9
references: 11287559
references: J Fish Dis. 2008 Nov;31(11):811-23
references: 18681902
references: J Virol. 1999 Dec;73(12):10387-98
references: 10559357
references: J Virol. 1992 Dec;66(12):7121-7
references: 1433509
references: J Biol Chem. 2012 Oct 19;287(43):36229-38
references: 22915590
references: Proc Natl Acad Sci U S A. 2011 May 10;108(19):7872-7
references: 21518887
references: J Mol Biol. 2006 Feb 3;355(5):942-56
references: 16343528
references: J Virol. 2001 Apr;75(8):3706-18
references: 11264360
references: J Virol. 1993 Aug;67(8):5003-11
references: 8392625
references: Emerg Infect Dis. 2007 May;13(5):764-7
references: 17553261
references: Virology. 1989 May;170(1):19-30
references: 2524126
references: Cytokine Growth Factor Rev. 2014 Oct;25(5):543-50
references: 24909568
references: J Virol. 2004 May;78(10):4953-64
references: 15113874
references: Viral Immunol. 2002;15(1):53-76
references: 11952147
references: J Virol. 2014 Apr;88(8):4251-64
references: 24478444
references: J Virol. 2006 Oct;80(20):9962-9
references: 17005674
references: RNA. 2001 Nov;7(11):1638-51
references: 11720292
references: J Virol. 2007 May;81(9):4412-21
references: 17301144
references: Eur J Biochem. 1992 Sep 15;208(3):581-7
references: 1396664
references: Virology. 2006 Feb 20;345(2):520-31
references: 16297426
references: Emerg Infect Dis. 2013 Feb;19(2):194-201; quiz 352
references: 23343480
references: Nucleic Acids Res. 2014 Mar;42(5):3228-45
references: 24371270
references: J Virol. 2003 Feb;77(4):2301-9
references: 12551967
references: PLoS Pathog. 2013;9(8):e1003591
references: 24009512
references: Emerg Infect Dis. 2008 Mar;14(3):416-22
references: 18325256
references: Virus Genes. 2008 Apr;36(2):313-21
references: 18264748
references: Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14622-7
references: 22908261
references: J Mol Biol. 1982 Apr 25;156(4):719-30
references: 6288962
references: J Virol. 1976 Nov;20(2):446-64
references: 978799
references: J Virol. 1993 Mar;67(3):1269-77
references: 7679745
references: J Virol. 2005 Jun;79(12):7597-608
references: 15919912
references: J Virol. 2001 Apr;75(8):3509-19
references: 11264340
references: Virology. 2009 Apr 25;387(1):211-21
references: 19278709
references: J Virol. 1990 Apr;64(4):1465-76
references: 2319643
references: J Virol. 1999 May;73(5):4316-26
references: 10196330
references: J Virol. 2004 Aug;78(16):8455-67
references: 15280454
references: Science. 2005 Sep 2;309(5740):1577-81
references: 16141076
references: Virology. 1981 Mar;109(2):281-9
references: 6259811
references: J Virol. 1990 Sep;64(9):4162-8
references: 2384916
references: J Virol. 1992 Feb;66(2):1007-15
references: 1731089
references: J Virol. 1999 Dec;73(12):10440-6
references: 10559362
references: J Virol. 2014 Jul;88(14):8065-76
references: 24807715
references: PLoS Pathog. 2012;8(5):e1002698
references: 22589727
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: Virology. 2009 Feb 5;384(1):201-8
references: 19036396
references: Nature. 2010 Nov 18;468(7322):452-6
references: 21085181
references: J Virol. 2008 Nov;82(21):10634-46
references: 18768986
references: Virology. 2013 Jul 5;441(2):171-81
references: 23601784
references: Front Genet. 2014 Feb 18;5:23
references: 24600468
references: J Virol. 2009 Sep;83(17):8327-39
references: 19515761
references: J Virol. 2005 Apr;79(8):4630-9
references: 15795249
references: J Virol. 1998 Dec;72(12):10286-91
references: 9811777
references: J Virol. 2013 Sep;87(18):9997-10003
references: 23824812