Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An essential step in the replication cycle of all retroviruses is the dimerization of genomic RNA prior to or during encapsidation and budding. In HIV-1, a stem-loop structure in the genomic RNA called the dimerization initiation site, or DIS, has been well characterized. However, the identification of the structure(s) necessary for dimerization of HIV-2 genomic RNA has been less straightforward, as reflected by recent conflicting reports. Here, using a variety of mutant and wild-type RNA constructs and a systematic analysis of experimental conditions, we demonstrate that two dimerization sites in HIV-2 RNA are clearly discernible under different experimental conditions. A short sequence overlapping the primer binding site acts as the default dimerization site for wild-type viral RNA transcripts of several lengths provided that dimerization incubation conditions do not include a high heat step (>50 degrees C), and electrophoresis is carried out under mild conditions that do not deplete the RNA of magnesium. However, some RNA constructs are able to dimerize through stem-loop 1 (SL1), which is the structure homologous to the HIV-1 DIS, under certain experimental conditions. Interestingly, deletion or mutation of the default PBS dimerization site leads to efficient usage of the SL1 dimerization site. This study defines conditions under which each site may be used for dimerization and demonstrates, furthermore, the facility with which the two sites can substitute for each other. This is suggestive of a switching mechanism that may be used in the viral replication cycle.
 ...
PMID:Alternate usage of two dimerization initiation sites in HIV-2 viral RNA in vitro. 1205 60

A large proportion of the plant LTR (Long Terminal Repeat) retrotransposons are partly or completely unable to synthesize their own machinery for transposition. However, most of these inactive or non-autonomous elements are likely able to retrotranspose, based on their insertional polymorphism. Therefore, they must be parasitic on one or more active partners. Here, we describe the parasitism of the chimeric BARE-2 element on the active BARE-1 (Barley RetroElement-2 and -1 respectively). These two elements are present in the Triticeae and related species, and are together polymorphic among closely related accessions. BARE-2 elements are unable to synthesize their own GAG protein, and harbor a specific ATG deletion in the gag ORF. However, BARE-2 sequences are conserved with BARE-1 in the PBS (Primer Binding Site), PSI (Packaging SIgnal) and DIS (DImerization Signal) domains. As these motifs have been shown to allow parasitism among the lentiviruses, we conclude that BARE-2 is probably a partial parasite of the BARE-1 element because the machinery of the latter can complement the defective GAG of the former. This example emphasizes that we must characterize the parasitic network of LTR retrotransposons and its implication for integration of autonomous, inactive, and non-autonomous elements in order to understand current and past host genome evolution.
 ...
PMID:Life without GAG: the BARE-2 retrotransposon as a parasite's parasite. 1710 63

In addition to genomic RNA, HIV-1 particles package cellular and spliced viral RNAs. In order to determine the encapsidation mechanisms of these RNAs, we determined the packaging efficiencies and specificities of genomic RNA, singly and fully spliced HIV mRNAs and different host RNAs species: 7SL RNA, U6 snRNA and GAPDH mRNA using RT-QPCR. Except GAPDH mRNA, all RNAs are selectively encapsidated. Singly spliced RNAs, harboring the Rev-responsible element, and fully spliced viral RNAs, which do not contain this motif, are enriched in virions to similar levels, even though they are exported from the nucleus by different routes. Deletions of key motifs (SL1 and/or SL3) of the packaging signal of genomic RNA indicate that HIV and host RNAs are encapsidated through independent mechanisms, while genomic and spliced viral RNA compete for the same trans-acting factor due to the presence of the 5' common exon containing the TAR, poly(A) and U5-PBS hairpins. Surprisingly, the RNA dimerization initiation site (DIS/SL1) appears to be the main packaging determinant of genomic RNA, but is not involved in packaging of spliced viral RNAs, suggesting a functional interaction with intronic sequences. Active and selective packaging of host and spliced viral RNAs provide new potential functions to these RNAs in the early stages of the virus life cycle.
 ...
PMID:HIV controls the selective packaging of genomic, spliced viral and cellular RNAs into virions through different mechanisms. 1742 27