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YADD mutants of human immunodeficiency virus type 1 and Moloney murine leukemia virus reverse transcriptase are resistant to lamivudine triphosphate (3TCTP) in vitro.
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Paul L. Boyer Hong-Qiang Gao Patrick K. Clark Stefan G. Sarafianos Edward Arnold Stephen H. Hughes 《Journal of virology》2001,75(14):6321-6328
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Guan Wang Yang Yang Xiaolan Huang 《Journal of biomolecular structure & dynamics》2013,31(7):1547-1557
?1 programmed ribosomal frameshifting (PRF) in viruses is often stimulated by a pseudoknot downstream from the slippery sequence. At the PRF junction of HIV-1, transmissible gastroenteritis virus (TGEV), Barmah Forest virus (BFV), Fort Morgan virus (FMV), and Equine arteritis virus (EAV), we identified potential double pseudoknots in either a tandem mode or embedded mode. In viruses with tandem pseudoknots (5′PK & 3′PK), the slippery sequence is encompassed in the 5′PK. The ribosome needs to unwind the 5′PK to get to the slippery sequence. In HIV-1, the 3′PK and several alternative structures are mutually exclusive. Disruption of the tandem pseudoknots may enable one of the alternative structures to form as the effective frameshift stimulator. In TGEV/BFV/FMV, the 3′PK is a conventional frameshift stimulator. In all cases, the tandem pseudoknots may slow down the ribosome before it reaches the conventional PRF signals. In EAV, a compact pseudoknot is embedded within loop2 of the otherwise conventional frameshift-stimulating pseudoknot. All double pseudoknots have the potential to stack their stems coaxially. We built structural models of the HIV-1 and EAV double pseudoknots to show that both the tandem and embedded modes are feasible and reasonable. We hypothesize that the fundamental reason for the viruses to utilize coaxially stacked double pseudoknots is to increase the overall stability of the frameshift regulating structure, and avoid an ultra-stable single pseudoknot which may become a ribosomal roadblock. Our results significantly expand the repertoire of RNA structures and dynamics that may potentially involve in ?1 PRF regulation. 相似文献
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Influenza A virus subtype H5N1 is highly contagious among birds, causing high mortality among domestic poultry. The viral genome is
contained on eight single RNA strands of which HA encode the antigenic glycoprotein called hemagglutinin. Hemagglutinin found on the surface
of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Among the most prevalent RNA structures the
pseudoknot motif represents an important piece of RNA architecture, as it provides a means for a single RNA strand to fold upon itself to produce
a globular structure capable of performing important biological functions. In this analysis we have identified the pseudoknot motifs in the
hemagglutinin gene of HPAI A (H5N1) Asian strains. Specific aptamers have been designed against these pseudoknots. These in-silico aptamers
can be used to hinder the ability of pseudoknots to facilitate ribosomal frameshifting. This may ultimately lead to reduce the coding efficiency of
the HA that encodes hemagglutinin and might be used as molecular medicine for H5N1. 相似文献
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Klarmann GJ Smith RA Schinazi RF North TW Preston BD 《The Journal of biological chemistry》2000,275(1):359-366
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We screened two independent RNA libraries consisting of molecules of 50 nucleotides of random sequence, one of which had additional viral psi-sequences to isolate RNA aptamers that bound to the mature form of the nucleocapsid (NC) protein of Human Immunodeficiency Virus Type-1 (HIV-1). Surface Plasmon Resonance measurements and gel shift assays showed that the RNA aptamers bound with high affinity and specificity. We employed RNase footprinting to characterize the RNA structures and to map their protein binding sites. Most of the selected RNA aptamers contained a plausible pseudoknot in addition to the characteristic stem-loop structure. Moreover, the pseudoknots were part of the NC binding sites. We propose that higher order structures such as pseudoknots may constitute binding motifs for nucleic acid binding proteins, especially for NC protein, which is a nucleic acid chaperone. 相似文献
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