The retroviral psi packaging element, also known as the Ψ RNA packaging signal, is a cis-acting RNA element identified in the genomes of the retroviruses Human immunodeficiency virus (HIV)[1] and Simian immunodeficiency virus (SIV).[2] It is involved in regulating the essential process of packaging the retroviral RNA genome into the viral capsid during replication.[3][4][5][6] The final virion contains a dimer of two identical unspliced copies of the viral genome.
| 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-regp |
| Domain(s) | Viruses |
| SO | SO:0000233 |
| PDB structures | PDBe |
In HIV, the psi element is around 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 mutagenesis 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 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
edit- ^ 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): 4085–4087. doi:10.1128/JVI.63.9.4085-4087.1989. PMC 251012. PMID 2760989.
- ^ 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): 2423–2430. doi:10.1099/vir.0.19185-0. PMID 12917463.
- ^ 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): 2050–2058. doi:10.1128/JVI.71.3.2050-2058.1997. PMC 191293. PMID 9032337.
- ^ 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): 4544–4554. doi:10.1128/JVI.71.6.4544-4554.1997. PMC 191676. PMID 9151848.
- ^ 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): 2963–2973. doi:10.1128/JVI.70.5.2963-2973.1996. PMC 190155. PMID 8627772.
- ^ Lever AM (2007). "HIV‐1 RNA Packaging". HIV‐1: Molecular Biology and Pathogenesis Viral Mechanisms, Second Edition. Advances in Pharmacology. Vol. 55. pp. 1–32. doi:10.1016/S1054-3589(07)55001-5. ISBN 978-0-12-373610-9. PMID 17586311.
- ^ 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): 583–592. doi:10.1093/jb/mvi158. PMID 16272570.
- ^ 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): 529–542. doi:10.1016/S0022-2836(02)01305-0. PMID 12559920.
- ^ 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.
- ^ 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): 877–893. doi:10.1006/jmbi.2000.3611. PMID 10736224.
- ^ 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): 801–818. doi:10.1006/jmbi.1998.2046. PMID 9743628.
- ^ Kerwood DJ, Cavaluzzi MJ, Borer PN (2001). "Structure of SL4 RNA from the HIV-1 packaging signal". Biochemistry. 40 (48): 14518–14529. doi:10.1021/bi0111909. PMID 11724565.
- ^ Berkhout, B; Van Wamel, JL (1996). "Role of the DIS hairpin in replication of human immunodeficiency virus type 1". Journal of Virology. 70 (10): 6723–6732. doi:10.1128/JVI.70.10.6723-6732.1996. PMC 190715. PMID 8794309.
- ^ 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. Bibcode:1994PNAS...91.4945S. doi:10.1073/pnas.91.11.4945. PMC 43906. PMID 8197162.
- ^ 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): 40385–40391. doi:10.1074/jbc.M301041200. PMID 12851400.
- ^ 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. Bibcode:1989PNAS...86.1495F. doi:10.1073/pnas.86.5.1495. PMC 286723. PMID 2784208.
- ^ 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.