Retroviral psi packaging element
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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 | |
---|---|
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.