title: The HIV-2 Rev-response element: determining secondary structure and defining folding intermediates.
abstract: Interaction between the viral protein Rev and the RNA motifs known as Rev response elements (RREs) is required for transport of unspliced and partially spliced human immunodeficiency virus (HIV)-1 and HIV-2 RNAs from the nucleus to the cytoplasm during the later stages of virus replication. A more detailed understanding of these nucleoprotein complexes and the host factors with which they interact should accelerate the development of new antiviral drugs targeting cis-acting RNA regulatory signals. In this communication, the secondary structures of the HIV-2 RRE and two RNA folding precursors have been identified using the SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) chemical probing methodology together with a novel mathematical approach for determining the secondary structures of RNA conformers present in a mixture. A complementary chemical probing technique was also used to support these secondary structure models, to confirm that the RRE2 RNA undergoes a folding transition and to obtain information about the relative positioning of RRE2 substructures in three dimensions. Our analysis collectively suggests that the HIV-2 RRE undergoes two conformational transitions before assuming the energetically most favorable conformer. The 3D models for the HIV-2 RRE and folding intermediates are also presented, wherein the Rev-binding stem-loops (IIB and I) are located coaxially in the former, which is in agreement with previous models for HIV-1 Rev-RRE binding.
authors: HIV Drug Resistance Program, Reverse Transcriptase Biochemistry Section, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors: Sabrina
authors: S
authors: Lusvarghi
authors: Joanna
authors: J
authors: Sztuba-Solinska
authors: Katarzyna J
authors: KJ
authors: Purzycka
authors: Gary T
authors: GT
authors: Pauly
authors: Jason W
authors: JW
authors: Rausch
authors: Stuart F J Le
authors: SF
authors: Grice
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D015498:HIV-2 / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D012367:RNA, Viral / Q000737:chemistry*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral; C038200:methidiumpropyl-EDTA-iron(II); D054321:rev Gene Products, Human Immunodeficiency Virus; C514861:rev protein, Human Immunodeficiency Virus-2; D004492:Edetic Acid
references: J Mol Biol. 1997 Mar 14;266(5):950-62
references: 9086273
references: Biochem J. 1970 Aug;118(5):810-2
references: 5476723
references: Nucleic Acids Res. 2012 Aug;40(14):e112
references: 22539264
references: BMC Bioinformatics. 2010 Mar 15;11:129
references: 20230624
references: Nat Protoc. 2006;1(3):1610-6
references: 17406453
references: Cell. 1989 Jun 30;57(7):1155-65
references: 2736624
references: Mol Cell. 2001 Mar;7(3):603-14
references: 11463385
references: Methods. 2010 Oct;52(2):150-8
references: 20554050
references: Cell. 1997 Sep 19;90(6):1051-60
references: 9323133
references: Trends Biochem Sci. 2003 Aug;28(8):419-24
references: 12932730
references: RNA. 2008 Oct;14(10):1979-90
references: 18772246
references: Nat Struct Mol Biol. 2010 Nov;17(11):1337-42
references: 20953181
references: Biochemistry. 1994 Aug 23;33(33):9831-44
references: 8060991
references: Proc Natl Acad Sci U S A. 1989 Nov;86(21):8222-6
references: 2682638
references: Science. 1996 Sep 13;273(5281):1547-51
references: 8703216
references: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14365-70
references: 18776047
references: AIDS Res Hum Retroviruses. 2003 Jul;19(7):569-74
references: 12908934
references: J Virol. 1990 Sep;64(9):4428-37
references: 2200888
references: Annu Rev Microbiol. 1998;52:491-532
references: 9891806
references: J Am Chem Soc. 2009 Feb 25;131(7):2541-6
references: 19193004
references: Mol Cell. 2008 Sep 26;31(6):824-34
references: 18922466
references: RNA. 2000 Feb;6(2):282-95
references: 10688366
references: J Mol Biol. 1994 Aug 12;241(2):193-207
references: 8057359
references: Nature. 1986 May 22-28;321(6068):412-7
references: 3012355
references: Acc Chem Res. 2011 Dec 20;44(12):1280-91
references: 21615079
references: Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5810-4
references: 20231488
references: J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Dec 15;13(5):403-7
references: 8970465
references: J Virol. 1991 Apr;65(4):2131-4
references: 2002556
references: BMC Bioinformatics. 2010 May 06;11:231
references: 20459631
references: Semin Cell Dev Biol. 1997 Feb;8(1):83-90
references: 15001110
references: Viruses. 2011 May;3(5):484-92
references: 21941623
references: Science. 1990 Feb 16;247(4944):845-8
references: 2406903
references: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1404-8
references: 19164515
references: Curr Protoc Bioinformatics. 2006 Mar;Chapter 12:Unit 12.6
references: 18428759
references: Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):683-7
references: 1992459
references: RNA Biol. 2012 Jan;9(1):6-11
references: 22258145
references: J Virol. 1992 Jul;66(7):4288-94
references: 1602545
references: Nucleic Acids Res. 2008 Jun;36(11):e63
references: 18477638
references: Biochemistry. 1989 Feb 21;28(4):1892-7
references: 2655698
references: Cell. 1990 Feb 23;60(4):675-83
references: 2406030
references: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12481-6
references: 20616058
references: J Am Chem Soc. 2005 Mar 30;127(12):4223-31
references: 15783204
references: Nature. 2009 Aug 6;460(7256):711-6
references: 19661910
references: Mol Biol Int. 2012;2012:530754
references: 22685659