Nucleic Acids Research, 2002, Vol. 30, No. 12 2647-2655
© 2002 Oxford University Press
Regulated HIV-2 RNA dimerization by means of alternative RNA conformations
1Department of Molecular and Structural Biology, Aarhus University, Denmark and 2Department of Human Retrovirology, Academic Medical Center K3-106, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands
The dimer initiation site (DIS) hairpin of the HIV-2 untranslated leader RNA mediates in vitro dimerization through ‘loop–loop kissing’ of a loop-exposed palindrome sequence. Premature RNA dimerization must be prevented during the retroviral life cycle. A regulatory mechanism has been proposed for the HIV-1 leader RNA that can adopt an alternative conformation in which the DIS motif is effectively masked by long-distance base pairing with upstream leader sequences. We now report that HIV-2 RNA dimerization is also regulated. Sequestering of the DIS motif by base pairing interactions with downstream leader sequences mediates a switch to a dimerization-impaired conformation. The existence of two alternative conformations of the HIV-2 leader RNA is supported by UV melting experiments. Furthermore, the equilibrium between the two conformations can be shifted by annealing of antisense oligonucleotides or by deletion of certain leader regions. These measures have a profound impact on the dimerization properties of the transcript, demonstrating a mutual exclusivity between the alternative conformation and dimerization, similar to what has been described for the HIV-1 leader. The overall resemblance in regulation of HIV-1 and HIV-2 RNA dimerization suggests that a similar mechanism may be operating in other lentiviruses and perhaps all retroviridae.
* To whom correspondence should be addressed. Tel: +31 20 5664822; Fax: +31 20 6916531; Email: b.berkhout@amc.uva.nl
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Centlivre, B. Klaver, B. Berkhout, and A. T. Das Functional Analysis of the Complex trans-Activating Response Element RNA Structure in Simian Immunodeficiency Virus J. Virol., September 15, 2008; 82(18): 9171 - 9178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. James and B. Sargueil RNA secondary structure of the feline immunodeficiency virus 5'UTR and Gag coding region Nucleic Acids Res., August 1, 2008; 36(14): 4653 - 4666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. Baig, J.-M. Lanchy, and J. S. Lodmell HIV-2 RNA dimerization is regulated by intramolecular interactions in vitro RNA, August 1, 2007; 13(8): 1341 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Lanchy and J. S. Lodmell An Extended Stem-Loop 1 Is Necessary for Human Immunodeficiency Virus Type 2 Replication and Affects Genomic RNA Encapsidation J. Virol., April 1, 2007; 81(7): 3285 - 3292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Pachulska-Wieczorek, K. J. Purzycka, and R. W. Adamiak New, extended hairpin form of the TAR-2 RNA domain points to the structural polymorphism at the 5' end of the HIV-2 leader RNA Nucleic Acids Res., May 31, 2006; 34(10): 2984 - 2997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. van den Born, C. C. Posthuma, A. P. Gultyaev, and E. J. Snijder Discontinuous Subgenomic RNA Synthesis in Arteriviruses Is Guided by an RNA Hairpin Structure Located in the Genomic Leader Region J. Virol., May 15, 2005; 79(10): 6312 - 6324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ooms, H. Huthoff, R. Russell, C. Liang, and B. Berkhout A Riboswitch Regulates RNA Dimerization and Packaging in Human Immunodeficiency Virus Type 1 Virions J. Virol., October 1, 2004; 78(19): 10814 - 10819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Lanchy, Q. N. Szafran, and J. S. Lodmell Splicing affects presentation of RNA dimerization signals in HIV-2 in vitro Nucleic Acids Res., August 27, 2004; 32(15): 4585 - 4595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ooms, K. Verhoef, E. Southern, H. Huthoff, and B. Berkhout Probing alternative foldings of the HIV-1 leader RNA by antisense oligonucleotide scanning arrays Nucleic Acids Res., February 3, 2004; 32(2): 819 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gallego, J. Greatorex, H. Zhang, B. Yang, S. Arunachalam, J. Fang, J. Seamons, S. Lea, R. J. Pomerantz, and A. M. L. Lever Rev Binds Specifically to a Purine Loop in the SL1 Region of the HIV-1 Leader RNA J. Biol. Chem., October 10, 2003; 278(41): 40385 - 40391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. LANCHY, J. D. IVANOVITCH, and J. S. LODMELL A structural linkage between the dimerization and encapsidation signals in HIV-2 leader RNA RNA, August 1, 2003; 9(8): 1007 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. G. Dirac, H. Huthoff, J. Kjems, and B. Berkhout Requirements for RNA heterodimerization of the human immunodeficiency virus type 1 (HIV-1) and HIV-2 genomes J. Gen. Virol., October 1, 2002; 83(10): 2533 - 2542. [Abstract] [Full Text] [PDF]
|
|