Retroviral Psi packaging element

Human immunodeficiency virus type 1 dimerisation initiation site
Predicted secondary structure and sequence conservation of HIV-1_DIS
Identifiers
Symbol HIV-1_DIS
Alt. Symbols Retroviral_psi
Rfam RF00175
Other data
RNA type Cis-reg
Domain(s) Viruses
SO 0000233

Retroviral Psi packaging element is a cis-acting RNA element identified in the genomes of the retroviruses Human immunodeficiency virus (HIV) [2] and Simian immunodeficiency virus (SIV). [3] It is involved in regulating the essential process of packaging the retroviral RNA genome into the viral capsid during replication.[4][5] [6][7] The final virion contains a dimer of two identical unspliced copies of the viral genome.

In HIV, the Psi element is ∼80–150 nucleotides in length, and located at the 5' end of the genome just upstream of the gag initiation codon.[8] It has a known secondary structure composed of four hairpins called SL1 to SL4 (SL is for Stem-loop) which are connected by relatively short linkers. All four stem loops are important for genome packaging and each of the stem loops SL1 [8] , SL2 [9],SL3 [10][11] and SL4 [12] has been independently expressed and structurally characterised.

Stem loop 1 (SL1) (also referred to as HIV-1_DIS) consists of a conserved hairpin structure with a palindromic loop sequence which was predicted and confirmed by mutagenesis.[13] This palindromic loop is known as the primary dimer initiation site (DIS) as it is believed to promote dimerization of the viral genome through formation of a “kissing dimer” intermediate. [14] The Rfam structure shown is based on a covariation model.

It has been shown that SL1 may provide a secondary binding site for the viral Rev protein. [15] The Rev protein is an essential HIV regulatory protein which increases the stability and transport of the unspliced viral RNA.[16]

Stem-loop 2 (SL2) (also referred to as HIV-1 SD) consists of a highly conserved 19 nt stem-loop which has been shown by mutatagenis to modulate the splicing efficiency of HIV-1 mRNAs. [17]

Stem-loop 3 (SL3) consists of a highly conserved 14 nt stem-loop which was predicted and confirmed by mutagenesis and mass spectrometric detection (MS3D). HIV-1 SL3 is sufficient by itself to induce heterologous RNA into virus-like particles but its deletion does not completely eliminate encapsidation. [17]

Stem-loop 4 (SL4) consists of a highly conserved 14 nt stem-loop that is located just downstream of the gag start codon. The structure was confirmed by mutagenesis and has an NMR and mass spectrometric detection (MS3D).[17] It also may have coding and non-coding roles.

References

  1. ^ Baba S, Takahashi K, Noguchi S, Takaku H, Koyanagi Y, Yamamoto N, Kawai G (2005). "Solution RNA structures of the HIV-1 dimerization initiation site in the kissing-loop and extended-duplex dimers.". J Biochem 138 (5): 583–92. doi:10.1093/jb/mvi158. PMID 16272570. 
  2. ^ Lever A, Gottlinger H, Haseltine W, Sodroski J (1989). "Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions". J Virol 63 (9): 4085–7. PMC 251012. PMID 2760989. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=251012. 
  3. ^ Strappe PM, Greatorex J, Thomas J, Biswas P, McCann E, Lever AM (2003). "The packaging signal of simian immunodeficiency virus is upstream of the major splice donor at a distance from the RNA cap site similar to that of human immunodeficiency virus types 1 and 2". J Gen Virol 84 (9): 2423–30. doi:10.1099/vir.0.19185-0. 
  4. ^ McBride MS, Panganiban AT (1997). "Position dependence of functional hairpins important for human immunodeficiency virus type 1 RNA encapsidation in vivo". J. Virol. 71 (3): 2050–8. PMC 191293. PMID 9032337. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=191293. 
  5. ^ McBride MS, Schwartz MD, Panganiban AT (1997). "Efficient encapsidation of human immunodeficiency virus type 1 vectors and further characterization of cis elements required for encapsidation". J. Virol. 71 (6): 4544–54. PMC 191676. PMID 9151848. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=191676. 
  6. ^ McBride MS, Panganiban AT (1996). "The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures". J. Virol. 70 (5): 2963–73. PMC 190155. PMID 8627772. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=190155. 
  7. ^ Lever AM (2007). "HIV-1 RNA packaging". Adv. Pharmacol. Advances in Pharmacology 55: 1–32. doi:10.1016/S1054-3589(07)55001-5. ISBN 9780123736109. PMID 17586311. 
  8. ^ a b Lawrence DC, Stover CC, Noznitsky J, Wu Z, Summers MF (2003). "Structure of the intact stem and bulge of HIV-1 Psi-RNA stem-loop SL1". J. Mol. Biol. 326 (2): 529–42. doi:10.1016/S0022-2836(02)01305-0. PMID 12559920. 
  9. ^ Amarasinghe GK, De Guzman RN, Turner RB, Chancellor KJ, Wu ZR, Summers MF (2000). "NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the psi-RNA packaging signal. Implications for genome recognition". J. Mol. Biol. 301 (2): 491–511. doi:10.1006/jmbi.2000.3979. PMID 10926523. 
  10. ^ Zeffman A, Hassard S, Varani G, Lever A (2000). "The major HIV-1 packaging signal is an extended bulged stem loop whose structure is altered on interaction with the Gag polyprotein". J Mol Biol 297 (4): 877–93. doi:10.1006/jmbi.2000.3611. PMID 10736224. 
  11. ^ Pappalardo L, Kerwood DJ, Pelczer I, Borer PN (1998). "Three-dimensional folding of an RNA hairpin required for packaging HIV-1". J. Mol. Biol. 282 (4): 801–18. doi:10.1006/jmbi.1998.2046. PMID 9743628. 
  12. ^ Kerwood DJ, Cavaluzzi MJ, Borer PN (2001). "Structure of SL4 RNA from the HIV-1 packaging signal". Biochemistry 40 (48): 14518–29. doi:10.1021/bi0111909. PMID 11724565. 
  13. ^ Berkhout, B; Van Wamel, JL (1996). "Role of the DIS hairpin in replication of human immunodeficiency virus type 1". Journal of virology 70 (10): 6723–32. PMC 190715. PMID 8794309. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=190715. 
  14. ^ Skripkin, E.; Paillart, J. C.; Marquet, R.; Ehresmann, B.; Ehresmann, C. (1994). "Identification of the primary site of the human immunodeficiency virus type 1 RNA dimerization in vitro". Proceedings of the National Academy of Sciences of the United States of America 91 (11): 4945–4949. PMC 43906. PMID 8197162. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43906.  edit
  15. ^ Gallego J, Greatorex J, Zhang H et al. (2003). "Rev binds specifically to a purine loop in the SL1 region of the HIV-1 leader RNA". J. Biol. Chem. 278 (41): 40385–91. doi:10.1074/jbc.M301041200. PMID 12851400. 
  16. ^ Felber, B. K.; Hadzopoulou-Cladaras, M.; Cladaras, C.; Copeland, T.; Pavlakis, G. N. (1989). "Rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA". Proceedings of the National Academy of Sciences of the United States of America 86 (5): 1495–1499. PMC 286723. PMID 2784208. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=286723.  edit
  17. ^ a b c Abbink, T. E. M.; Berkhout, B. (2007). "RNA Structure Modulates Splicing Efficiency at the Human Immunodeficiency Virus Type 1 Major Splice Donor". Journal of Virology 82 (6): 3090–3098. doi:10.1128/JVI.01479-07. PMC 2258995. PMID 18160437. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2258995.  edit

External links

Gallery of HIV-1 Psi element stem loops 2-4
HIV-1_SD: Secondary structure taken from the Rfam database. Family RF01380  
HIV-1_SL3: Secondary structure taken from the Rfam database. Family RF01381  
HIV_SL4: Secondary structure taken from the Rfam database. Family RF01382