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At least 613 records · Page 34Linked to original sources
PubMed2004

Anti-termination by SIV Tat requires flexibility of the nascent TAR structure.

Substitution of the SIVmac239 promoter/enhancer by the strong EF1alpha promoter results in a severe replication defect due to a failure to respond to Tat. Revertant viruses with minimal promoter sequences (two Sp1 sites and a TATA box) were obtained that had fully restored their replicative potential. Comparison of the different LTRs indicated that structural alterations in the TAR stem due to a 31bp exon of the EF1alpha promoter rather than the mere presence of transcription factor binding sites within U3 were responsible for the attenuation. Structural models based on genuine RNA sequences combined with a refined algorithm to calculate the probability of the looping-mediated interaction between protein complexes bound to nucleic acid polymers indicated that the local concentration of TAR-bound Tat close to the RNA polymerase II complex was reduced more than 100-fold for the mutant as compared to SIVmac239. These results show that HIV/SIV replication requires only a minimal set of cis-acting elements in the promoter and suggest a hitherto unrecognised requirement of flexibility for the nascent TAR structure to allow anti-termination by Tat.

Amino Acid Sequence↗
PubMed2006

Fungicidal value of wood tar from pyrolysis of treated wood.

The objective of the paper was to estimate the fungicidal value of wood tar extracted as a product of pyrolysis of wood previously treated with either creosote oil or CCB-type salt preservative. The effectiveness of wood treated with one of these two wood tar residuals was compared to the effectiveness of wood treated with virgin creosote oil (type WEI-B) and an untreated control. Wood was impregnated with alcohol solutions of the two extracted preservatives or virgin creosote oil and then subjected to the Coniophora puteana, Poria placenta and Coriolus versicolor fungi. The fungicidal values of the investigated preservatives were determined with the use of the short agar-block method and the aging test according to the standard EN 84. It was found that wood tar extracted by pyrolysis of old creosote-treated wood and then used to treat wood may have potential as a preservative for wood protection or as a component of preservatives.

Basidiomycota↗
PubMed2000

The chromosomal protein HMG-D binds to the TAR and RBE RNA of HIV-1.

The high mobility group protein HMG-D is known to bind preferentially to DNA of irregular structures with little or no sequence specificity. Upon binding to DNA, this HMG-box protein widens the minor groove of the double helix and induces a significant bending of the helix. We show here that HMG-D can strongly bind to double-stranded RNA. Electrophoretic mobility shift assays show that HMG-D100 interacts with the transactivation response region (TAR) RNA from HIV-1. Strong interaction with a high affinity Rev protein binding element (RBE) RNA was also characterized. Gel shift experiments performed with several TAR RNA constructs lacking the lateral pyrimidine bulge or with modified apical loop regions indicate that the protein does not recognize the single-strand domains of the RNA but apparently interacts directly with the double-stranded stem regions. No protein-RNA complexes could be detected when using single-stranded oligoribonucleotides. HMG-D protein could bind to the wide minor groove of the A-form TAR RNA. The comparison of the amino acid sequence of HMG-D with that of known RNA binding proteins suggests that the interaction of the protein with a double-stranded RNA implicates the basic region of HMG-D as well as its HMG-box domain. From the in vitro data reported here, we propose a novel functional role for proteins of the HMG-1 family. The results suggest that architectural HMG proteins can be recruited by double-stranded RNA for the development of HIV-1 in the host cell.

Base Sequence↗
PubMed1995

Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs.

The RNA-binding activity of the interferon-inducible, RNA-dependent protein kinase PKR, expressed from the human PKR cDNA, was quantitated using a gel mobility-shift assay. The N-terminal R-domain truncation Wt(1-243) and the full-length catalytic mutant K296R(21-551) were analyzed for their abilities to bind adenovirus VAI RNA, human immunodeficiency virus TAR RNA, and the synthetic homopolymer pI:pC RNA. The N-terminal 243 amino acid residue form of PKR [Wt(1-243)] bound VAI RNA with similar affinity as the 551 amino acid residue full-length catalytic mutant [K296R(1-551)]. The dissociation constant for VAI RNA was approximately 2 x 10(-9) M for both the K296R(1-551) and Wt(1-243) proteins. The K64E mutation significantly impaired the VAI RNA-binding activity as measured with the full-length double-point mutant PKR protein, K64E/K296R(1-551). Using a gel-shift competition assay, the dissociation constants of K296R(1-551) and Wt(1-243) for VAI(1-160) RNA and pI:pC RNA were comparable. By contrast, the dissociation constants of K296R(1-551) and Wt(1-243) for TAR(1-82) RNA were both about 1 x 10(-7) M. These results suggest that the RNA-binding affinity of PKR is approximately 100-fold lower for TAR RNA than for either VAI RNA or pI:pC RNA and that the full-length and N-terminal R-domain forms of PKR bind RNA with similar affinity.

Adenoviridae↗
PubMed1997

Detection of specific human immunodeficiency virus type 1 Tat-TAR complexes in the presence of mild denaturing conditions.

Gene expression from the human immunodeficiency virus 1 (HIV-1) is greatly enhanced by binding of the virally encoded Tat protein to a 59-base RNA stem-loop structure, the Transactivation Responsive Element (TAR), located at the 5'-termini of all viral transcripts. This interaction was investigated in vitro using 32P-labelled TAR and highly purified Tat in which cysteine residues were blocked by sulpitolysis (S-Tat). It is shown that specific complex formation between S-Tat and TAR can occur in the presence of urea, with urea concentrations between 5 and 6 M causing an approximately two-fold increase in the level of binding. Two conditions favoring RNA secondary structure, low temperature (0 degree C) and the presence of divalent cations (Mg2+), diminished the level of specific binding. These observations suggest that the presence of mild denaturants promoted macromolecular refolding or rearrangement in a manner that increased the number of molecules available for binding, and present a general method for studying protein/RNA interactions where analysis has been obstructed by improper protein or RNA conformation.

Base Sequence↗
PubMed1996

Cloning and sequence analysis of the candidate nicotinic acetylcholine receptor alpha subunit gene tar-1 from Trichostrongylus colubriformis.

A T. colubriformis genomic library in lambda EMBL3 was screened for sequences homologous to the Caenorhabditis elegans unc-38 nicotinic acetylcholine receptor (nAChR) alpha-subunit gene. The candidate gene tar-1 (for Trichostrongylus acetylcholine receptor subunit gene 1) comprising 13704 base pairs was thus identified. BLAST comparison of the sequenced clone with GenBank, followed by comparison of translated regions in six reading frames with protein databases, identified clearly defined tracts corresponding to 12 putative exons sharing high sequence homology to other nAChR genes and able to code for sequential regions of a putative nAChR alpha-subunit protein (tar-1). Tar-1 shares sequence similarities with over 40 nAChR subunit proteins. The highest similarity (91.6%) is with unc-38, suggesting that nAChR sequences from nematodes are closely related. The sequence includes motifs typical of these molecules including adjacent cysteine residues at the ACh binding site and four transmembrane regions. The DNA sequence presents the longest genomic tract described for this organism and should prove useful as a probe source in the search for nAChR genes from this and other nematodes and for studying the molecular mechanism of resistance to levamisole, a drug which is known to act on nAChRs of worms and which is widely used for parasite control.

Amino Acid Sequence↗
PubMed1997

Specific isolation of human rDNA genes by TAR cloning.

Selective cloning of human DNA in YACs from monochromosomal human/rodent hybrid cells lines and radiation hybrids can be accomplished by transformation-associated recombination (TAR) between Alu-containing vector(s) and human DNA in yeast. We have expanded this approach to the specific isolation of repetitive genes from the human genome. Highly selective isolation of human rDNA was accomplished using total human DNA and a pair of differentially marked linear TAR cloning vectors where one contained a small fragment of a human rDNA repeat and the other had an Alu repeat as targeting sequences. About half the transformants that acquired both vectors markers had YACs with human rDNA inserts. These results suggest that TAR can be applied to the general isolation of gene families and amplified region from genomic DNAs.

Chromosomes, Artificial, Yeast↗
PubMed2002

Protective effect of quercetin against cigarette tar extract-induced impairment of erythrocyte deformability.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is one of the most abundant flavonol-type flavonoids rich in diet and suggested to possess a beneficial role in blood circulation. This study was conducted to know the effect of quercetin aglycone and one of its possible metabolite, quercetin-3-O-beta-D-glucuronide on cigarette tar extract-induced impairment of erythrocyte deformability. Erythrocyte suspension containing quercetin aglycone, quercetin-3-O-beta-D-glucuronide or quercetin-3-O-beta-D-glucoside was forced to flow through microchannels with equivalent diameter of 7 &mgr;m and its transit time was measured as an index of erythrocyte deformability using microchannel array method. Both quercetin aglycone and quercetin-3-O-beta-D-glucuronide, but not quercetin-3-O-beta-D-glucoside, substantially increased erythrocyte deformability indicating that the former two compounds affect the physicochemical state of erythrocyte by interacting with its membranes. Aqueous cigarette tar extract caused marked decrease in erythrocyte deformability with concomitant increase of membranous lipid peroxidation. In that case, quercetin aglycone suppressed the impairment of erythrocyte deformability as well as membranous lipid peroxidation. The same effect was found in quercetin-3-O-beta-D-glucuronide, eventhough its effect was lower than that of quercetin aglycone. Thus, not only quercetin aglycone but also its conjugate metabolite protects erythrocyte membrane from the damage of smoking by scavenging reactive oxygen species generated from cigarette tar. Intake of quercetin-rich food may be helpful to protect membranous damage in erythrocytes from smoking.

Journal Article↗
PubMed2002

Investigation of RNA-protein and RNA-metal ion interactions by electron paramagnetic resonance spectroscopy. The HIV TAR-Tat motif.

Electron paramagnetic resonance (EPR) spectroscopy was used to investigate changes in dynamics of spin-labeled nucleotides in the TAR RNA (U23, U25, U38, and U40) upon binding to cations, argininamide, and two peptides derived from the Tat protein. Nearly identical changes in dynamics were obtained for either calcium or sodium ions, indicating the absence of a calcium-specific structural change for the TAR RNA in solution that had previously been suggested by crystallographic data. Similar dynamic signatures were obtained for two Tat-derived peptides that have the same important binding determinant (R52) and similar binding affinities to the TAR RNA. However, U23 and U38 were substantially less mobile for the wild-type peptide (YGRKKRRQRRR) than for the mutant (YKKKKRKKKKA), demonstrating that, flanking R52, amino acids in the wild-type sequence make specific contacts to the RNA.

Arginine↗
PubMed1993

An NMR study of the HIV-1 TAR element hairpin.

The TAR hairpin is an important part of the 5' long terminal repeat of HIV-1 and appears to be recognized by a cellular protein. A 14-base model of the native TAR hairpin 5'-GAGC[CUGGGA]-GCUC-3' (loop bases in square brackets) has been studied by proton, phosphorus, and natural abundance carbon NMR; these results are compared to other published NMR studies of the TAR hairpin. Assignments of all nonexchangeable protons and of all the stem-exchangeable protons have been made, as well as all phosphorus and many carbon resonances. Large J1'2' and J3'4' proton-proton coupling in the C5, G8, and G9 sugars indicate an equilibrium between C2'- and C3'-endo forms; these data show a dynamic loop structure. We see three broad imino resonances that have not been reported before; these resonances are in the right region for unbonded loop imino protons. These peaks suggest the protons are protected from fast exchange with the solvent by the structure of the hairpin loop. Simulated annealing and molecular dynamics with 148 distance constraints, 11 hydrogen bonds, and 84 torsion angle constraints showed a wide variety of structures. Certain trends are evident, such as continuation of the A-form helix on the 3' side of the hairpin loop. The ensemble of calculated structures agree with most chemical modification data.

Base Sequence↗
PubMed2003

Selective binding of TAR RNA by a Tat-derived beta-peptide.

[structure: see text] The interaction between the HIV-1 Tat protein and the TAR RNA element in the nascent viral genomic transcript is required for viral replication. An 11-residue beta-peptide (1), an all-beta homologue of the Arg-rich region Tat 47-57, binds TAR RNA with K(d) = 29 +/- 4 nM. A control beta-peptide (2) in which all Arg side chains are replaced by Lys side chains shows increased affinity but decreased specificity for wild-type vs bulge-deleted TAR RNA, as do the alpha-peptide analogues of 1 and 2.

Amino Acid Sequence↗
PubMed1998

Mutational screening of thrombopoietin receptor gene (c-mpl) in patients with congenital thrombocytopenia and absent radii (TAR).

Thrombocytopenia with absent radii (TAR) is a rare autosomal recessive disease characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. We performed mutational screening of coding and promoter regions of the c-mpl gene, encoding thrombopoietin (TPO) receptor, by sequence analysis in four unrelated patients affected by TAR syndrome. Our results indicate that c-mpl gene mutations are not a common cause of thrombocytopenia in TAR syndrome.

Adolescent↗
PubMed2004

TAR syndrome with annular pancreas and anal atresia - a case report.

TAR syndrome is manifested by the presence of hypomegakaryocytic thrombocytopenia and the bilateral absence of radii. An 8-day-old female newborn was referred to our clinic with diagnosis of TAR syndrome and symptoms of intestinal obstruction. On perineal examination she also had anal atresia with rectovestibular fistula. Because of persistent bile-stained drainage from the nasogastric tube, an upper gastrointestinal contrast study was performed and partial duodenal obstruction was detected. At operation, an annular pancreas was encountered and side-to-side duodenoduodenostomy was performed. A small number of gastrointestinal system malformations associated with TAR syndrome has been reported. Our case is unique; the association with annular pancreas and anal atresia with rectovestibular fistula has never been previously reported.

Abnormalities, Multiple↗
PubMed2002

TAR RNA loop: a scaffold for the assembly of a regulatory switch in HIV replication.

Replication of HIV requires the Tat protein, which activates elongation of RNA polymerase II transcription at the HIV-1 promoter by interacting with the cyclin T1 (CycT1) subunit of the positive transcription elongation factor complex b (P-TEFb). The transactivation domain of Tat binds directly to the CycT1 subunit of P-TEFb and induces loop sequence-specific binding of P-TEFb onto nascent HIV-1 trans-activation responsive region (TAR) RNA. We used systematic RNA-protein photocross-linking, Western blot analysis, and protein footprinting to show that residues 252-260 of CycT1 interact with one side of the TAR RNA loop and enhance interaction of Tat residue K50 to the other side of the loop. Our results show that TAR RNA provides a scaffold for two protein partners to bind and assemble a regulatory switch in HIV replication. RNA-mediated assembly of RNA-protein complexes could be a general mechanism for stable ribonucleoprotein complex formation and a key step in regulating other cellular processes and viral replication.

Base Sequence↗
PubMed2002

A nucleolar TAR decoy inhibitor of HIV-1 replication.

Tat is a critical regulatory factor in HIV-1 gene expression. It mediates the transactivation of transcription from the HIV-1 LTR by binding to the transactivation response (TAR) element in a complex with cyclin T1. Because of its critical and early role in HIV gene expression, Tat and its interaction with the TAR element constitute important therapeutic targets for the treatment of HIV-1 infection. Based on the known nucleolar localization properties of Tat, we constructed a chimeric small nucleolar RNA-TAR decoy that localizes to the nucleoli of human cells and colocalizes in the nucleolus with a Tat-enhanced GFP fusion protein. When the chimeric RNA was stably expressed in human T lymphoblastoid CEM cells it potently inhibited HIV-1 replication. These results demonstrate that the nucleolar trafficking of Tat is critical for HIV-1 replication and suggests a role for the nucleolus in HIV-1 viral replication.

Anti-HIV Agents↗
PubMed2002

Subunit organization in a soluble complex of tar, CheW, and CheA by electron microscopy.

The Salmonella and Escherichia coli aspartate receptor, Tar, is representative of a large class of membrane receptors that generate chemotaxis responses by regulating the activity of an associated histidine protein kinase, CheA. Tar is composed of an NH(2)-terminal periplasmic ligand-binding domain linked through a transmembrane sequence to a COOH-terminal coiled-coil signaling domain in the cytoplasm. The isolated cytoplasmic domain of Tar fused to a leucine zipper sequence forms a soluble complex with CheA and the Src homology 3-like kinase activator, CheW. Activity of the CheA kinase in the soluble complex is essentially the same as in fully active complexes with the intact receptor in the membrane. The soluble complex is composed of approximately 28 receptor cytoplasmic domain chains, 6 CheW chains, and 4 CheA chains. It has a molecular weight of 1,400,000 (Liu, I., Levit, M., Lurz, R., Surette, M.G., and Stock, J.B. (1997) EMBO J. 16, 7231-7240). Electron microscopy reveals an elongated barrel-like structure with a largely hollow center. Immunoelectron microscopy has provided a general picture of the subunit and domain organization of the complex. CheA and CheW appear to be in the middle of the complex with the leucine zippers of the receptor construct at the ends. These findings show that the receptor signaling complex forms higher ordered structures with defined geometric architectures. Coupled with atomic models of the subunits, our results provide insights into the functional architecture by which the receptor regulates CheA kinase activity during bacterial chemotaxis.

Bacterial Proteins↗
PubMed2003

Rotational on-off switching of a hybrid membrane sensor kinase Tar-ArcB in Escherichia coli.

Signal transduction in biological systems typically involves receptor proteins that possess an extracytosolic sensory domain connected to a cytosolic catalytic domain. Relatively little is known about the mechanism by which the signal is transmitted from the sensory site to the catalytic site. At least in the case of Tar (methyl-accepting chemotaxis protein for sensing aspartate) of Escherichia coli, vertical piston-like displacements of one transmembrane segment relative to the other within the monomer induced by ligand binding has been shown to modulate the catalytic activity of the cytosolic domain. The ArcB sensor kinase of E. coli is a transmembrane protein without a significant periplasmic domain. Here, we explore how the signal is conveyed to the catalytic site by analyzing the property of various Tar-ArcB hybrids. Our results suggest that, in contrast to the piston-like displacement that operates in Tar, the catalytic activity of ArcB is set by altering the orientation of the cytosolic domain of one monomer relative to the other in the homodimer. Thus, ArcB represents a distinct family of membrane receptor proteins whose catalytic activity is determined by rotational movements of the cytosolic domain.

Amino Acid Sequence↗
PubMedDate not supplied

RNA and N3'-->P5' kissing aptamers targeted to the trans-activation responsive (TAR) RNA of the human immunodeficiency virus-1.

We used in vitro selection to identify RNA aptamers able to selectively bind to the TAR RNA motif of HIV-1, an unperfect RNA hairpin involved in the transcription of the retroviral genome. We selected aptameric RNA hairpins giving rise to kissing complexes with TAR. The N3'-->P5' phosphoramidate variant of the aptamer bind to TAR with a Kd in the low nanomolar range. However, only the RNA-RNA loop-loop complex is recognized by the Rop protein of E. coli which is specific for kissing complexes.

Bacterial Proteins↗