@article{f7bd263750ed48d5828ac6f45c9a1cbf,
title = "Regulation of primate lentiviral RNA dimerization by structural entrapment",
abstract = "Background: Genomic RNA dimerization is an important process in the formation of an infectious lentiviral particle. One of the signals involved is the stem-loop 1 (SL1) element located in the leader region of lentiviral genomic RNAs which also plays a role in encapsidation and reverse transcription. Recent studies revealed that HIV types 1 and 2 leader RNAs adopt different conformations that influence the presentation of RNA signals such as SL1. To determine whether common mechanisms of SL1 regulation exist among divergent lentiviral leader RNAs, here we compare the dimerization properties of SIVmac239, HIV-1, and HIV-2 leader RNA fragments using homologous constructs and experimental conditions. Prior studies from several groups have employed a variety of constructs and experimental conditions. Results: Although some idiosyncratic differences in the dimerization details were observed, we find unifying principles in the regulation strategies of the three viral RNAs through long- and short-range base pairing interactions. Presentation and efficacy of dimerization through SL1 depends strongly upon the formation or dissolution of the lower stem of SL1 called stem B. SL1 usage may also be down-regulated by long-range interactions involving sequences between SL1 and the first codons of the gag gene. Conclusion: Despite their sequence differences, all three lentiviral RNAs tested in this study showed a local regulation of dimerization through the stabilization of SL1.",
author = "Baig, {Tayyba T.} and Strong, {Christy L.} and Lodmell, {J. Stephen} and Lanchy, {Jean Marc}",
note = "Funding Information: We acknowledge Quenna N. Szafran for the initial experiments on SIV RNA constructs. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: p239SpSp5' ([28,29]) and p83-2 [30] from Dr Ronald Desrosiers. The pROD10 plasmids from Drs. J.-M. Bechet and A.M.L. Lever were obtained from the Centralised Facility for AIDS Reagents supported by EU Programme EVA (contract QLK2-CT-1999-00609) and the UK Medical Research Council. This research is supported by the National Institutes of Health grant number AI45388 to J.S.L. Funding Information: The extended stem B mutation was introduced into a 1– 444 HIV-2 ROD sequence using a modified antisense primer (HIV2 asMUT444Eco, Table 1). This mutation is a substitution of nts G437-T438 by the sequence CTTTCTA. DNA template plasmids containing the first 272, 277, or 373 nucleotides of HIV-1 NL4-3 genomic RNA and a T7 RNA polymerase promoter were constructed using a similar strategy (nt 1 of the genomic RNA sequence corresponds to nt 455 of [GenBank:AF324493]). The numbers used to define RNA constructs (for instance 1–561 HIV-2 RNA) are based on genomic RNA numbering. The HIV-2 ROD DNA template (modified plasmid pROD10) was provided by the EU Programme EVA/MRC Centralised Facility for AIDS Reagents, NIBSC, UK (Grant Number QLK2-CT-1999-00609 and GP828102). The SIV mac239 (p239SpSp5' plasmid) and HIV-1 (p83-2 plasmid) DNA templates were obtained from Dr. Ronald Desrosiers through the AIDS Research and Reference Reagent Program ([28-30]). The digested polymerase chain reaction",
year = "2008",
month = jul,
day = "17",
doi = "10.1186/1742-4690-5-65",
language = "English",
volume = "5",
journal = "Retrovirology",
issn = "1742-4690",
}
