A Chimeric Human Immunodeficiency Virus Type 1 TAR Region Which Mediates High Level Trans-activation in Both Rodent and Human Cells

Newstein, Michael; Lee, Im Soon; Venturini, Deborah S.; Shank, Peter R.

doi:10.1006/viro.1993.1665

Cited by 9 publications

(4 citation statements)

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“…6B). As reported by others (2,15,16,32,33,47,50), Tat was not active on the intact TAR element in mouse cells. We conclude that the MuLV R region cannot functionally substitute for the HIV TAR element.…”

Section: Secondary Structure Is Important For the Activity Of The Mulsupporting

confidence: 74%

The Secondary Structure of the R Region of a Murine Leukemia Virus Is Important for Stimulation of Long Terminal Repeat-Driven Gene Expression

Cupelli

Okenquist

Trubetskoy

et al. 1998

J Virol

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In addition to their role in reverse transcription, the R-region sequences of some retroviruses affect viral transcription. The first 28 nucleotides of the R region within the long terminal repeat (LTR) of the murine type C retrovirus SL3 were predicted to form a stem-loop structure. We tested whether this structure affected the transcriptional activity of the viral LTR. Mutations that altered either side of the stem and thus disrupted base pairing were generated. These decreased the level of expression of a reporter gene under the control of viral LTR sequences about 5-fold in transient expression assays and 10-fold in cells stably transformed with the LTR-reporter plasmids. We also generated a compensatory mutant in which both the ascending and descending sides of the stem were mutated such that the nucleotide sequence was different but the predicted secondary structure was maintained. Most of the activity of the wild-type SL3 element was restored in this mutant. Thus, the stem-loop structure was important for the maximum activity of the SL3 LTR. Primer extension analysis indicated that the stem-loop structure affected the levels of cytoplasmic RNA. Nuclear run-on assays indicated that deletion of the R region had a small effect on transcriptional initiation and no effect on RNA polymerase processivity. Thus, the main effect of the R-region element was on one or more steps that occurred after the template was transcribed by RNA polymerase. This finding implied that the main function of the R-region element involved RNA processing. R-region sequences of human immunodeficiency virus type 1 or mouse mammary tumor virus could not replace the SL3 element. R-region sequences from an avian reticuloendotheliosis virus partially substituted for the SL3 sequences. R-region sequences from Moloney murine leukemia virus or feline leukemia virus did function in place of the SL3 element. Thus, the R region element appears to be a general feature of the mammalian type C genus of retroviruses.

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Section: Secondary Structure Is Important For the Activity Of The Mulsupporting

confidence: 74%

The Secondary Structure of the R Region of a Murine Leukemia Virus Is Important for Stimulation of Long Terminal Repeat-Driven Gene Expression

Cupelli

Okenquist

Trubetskoy

et al. 1998

J Virol

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“…4B and 6B reveals a difference in trans-activation of HIV43(AP) 4 by RNA-targeted Tat and DNA-targeted Tat. These results suggest a deficient Tat-TAR interaction in S. cerevisiae as observed in rodent cells (41,42). In another context, an efficient Tat-TAR interaction has been detected in the three-hybrid system (86).…”

Section: Discussionmentioning

confidence: 68%

“…In vivo studies have shown that Tat functions only in mammalian cells and has a weak activity in rodent cells. These cells lack a cellular cofactor that allows a correct Tat-TAR interaction in vivo (41,42), and a newly identified protein, cyclin T, has the properties of this missing co-factor (43). No trans-activation of HIV-1 LTR by Tat has been detected in insect and yeast cells, but the defective steps have not been determined in these organisms (44,45).…”

Section: Cellular Context Is An Important Determinant For the Activitmentioning

confidence: 99%

Identification of Limiting Steps for Efficient Trans-activation of HIV-1 Promoter by Tat in Saccharomyces cerevisiae

Daviet¹,

Bois²,

Battisti³

et al. 1998

Journal of Biological Chemistry

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“…The spacings between the TAR bulge and loop, and between the Tat arginine-rich and activation domains, must be maintained for high activity (10,16,17), consistent with a model in which the loop-binding protein contacts both the TAR loop and the Tat activation domain, thereby increasing the affinity of the complex. RNA binding by the accessory protein does not appear to be required for Tat activation because replacing TAR and the Tat argininerich domain with other RNA-protein interactions, such as the R17 coat protein-RNA interaction, supports efficient Tat function both in human and in murine cells (18,19). Nevertheless, the cellular protein still may be recruited into the transcription complex in the absence of TAR through interactions with Tat.…”

mentioning

confidence: 99%

Altering the Context of an RNA Bulge Switches the Binding Specificities of Two Viral Tat Proteins

Smith

Crotty²,

Harada³

et al. 1998

Biochemistry

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The bovine immunodeficiency virus (BIV) Tat protein binds with high affinity to its TAR RNA site through a large set of specific RNA-protein contacts whereas human immunodeficiency virus (HIV) Tat makes relatively few contacts to HIV TAR and requires the assistance of a cellular protein to bind with high affinity. The two TAR sites are structurally very similar, but BIV Tat appears unable to make the same set of high-affinity contacts to HIV TAR. To determine the basis of this discrimination, we examined BIV Tat binding to a series of hybrid TARs both in vivo and in vitro. We expected that differences in the architectures of the bulges might account for the binding specificity; however, the results show that flanking base pairs provide the key determinants. Based on these data, we designed a novel TAR that is recognized by both BIV Tat and HIV Tat. This RNA may be viewed as a primordial TAR from which two distinct recognition strategies can be evolved.

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A Chimeric Human Immunodeficiency Virus Type 1 TAR Region Which Mediates High Level Trans-activation in Both Rodent and Human Cells

Cited by 9 publications

References 0 publications

The Secondary Structure of the R Region of a Murine Leukemia Virus Is Important for Stimulation of Long Terminal Repeat-Driven Gene Expression

The Secondary Structure of the R Region of a Murine Leukemia Virus Is Important for Stimulation of Long Terminal Repeat-Driven Gene Expression

Identification of Limiting Steps for Efficient Trans-activation of HIV-1 Promoter by Tat in Saccharomyces cerevisiae

Altering the Context of an RNA Bulge Switches the Binding Specificities of Two Viral Tat Proteins

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