Journal ArticleDOI
The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA.
TLDR
These results indicate that the HIV-1 rev gene product induces HIV- 1 structural gene expression by activating the sequence-specific nuclear export of incompletely spliced HIV-2 RNA species.Abstract:
HUMAN immunodeficiency virus type 1 (HIV-1) replication requires the expression of two classes of viral mRNA. The early class of HIV-1 transcripts is fully spliced and encodes viral regulatory gene products. The functional expression of one of these nuclear regulatory proteins, termed Rev (formerly Art or Trs), induces the cytoplasmic expression of the incompletely spliced, late class of HIV-1 mRNAs that encode the viral structural proteins, including Gag and Env1–6. Here, we provide evidence that this induction reflects the export from the cell nucleus to the cytoplasm of a pool of unspliced viral RNA constitutively expressed in the nucleus. The hypothesis that Rev acts on RNA transport, rather than splicing, is further supported by the observation that the cytoplasmic expression of a non-spliceable HIV-1 env gene sequence is also subject to Rev regulation. Here we show that this Rev response requires a specific target sequence which coincides with a complex RNA secondary structure present in the env gene. The response to Rev is fully maintained when this sequence is relocated to other exonic or intronic locations within env but is ablated by inversion. These results indicate that the HIV-1 rev gene product induces HIV-1 structural gene expression by activating the sequence-specific nuclear export of incompletely spliced HIV-1 RNA species.read more
Citations
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Journal ArticleDOI
Conserved structures and diversity of functions of RNA-binding proteins.
TL;DR: The major RNA-binding motifs are described and examples of how they may function are given.
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Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation
TL;DR: It is shown that disruption of the murine GSK-3β gene results in embryonic lethality caused by severe liver degeneration during mid-gestation, a phenotype consistent with excessive tumour necrosis factor (TNF) toxicity, as observed in mice lacking genes involved in the activation of the transcription factor activation NF-κB.
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Mechanisms of viral membrane fusion and its inhibition
Debra M. Eckert,Peter S. Kim +1 more
TL;DR: The fusion mechanism involves a transient conformational species that can be targeted by therapeutic strategies and is likely utilized by a wide variety of enveloped viruses for which similar therapeutic interventions should be possible.
Journal ArticleDOI
Nucleocytoplasmic Transport: The Soluble Phase
Iain W. Mattaj,Ludwig Englmeier +1 more
TL;DR: Directionality of either import or export depends on association between a substrate and its receptor on one side of the nuclear envelope and dissociation on the other, and the Ran GTPase is critical in generating this asymmetry.
Journal ArticleDOI
The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs.
TL;DR: The Rev activation domain constitutes a nuclear export signal that redirects RRE-containing viral RNAs to a non-mRNA export pathway.
References
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TL;DR: The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV-III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes.
Journal ArticleDOI
Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism
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