Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Rev protein of human immunodeficiency virus type 1 is a sequence-specific RNA binding protein that is essential for viral replication. Here we present evidence that Rev is a stable oligomer both in vitro and in vivo. Analysis of Rev mutants indicates that oligomerization is essential for RNA binding and hence Rev function. The oligomerization and RNA binding domains overlap over 47 amino acids. Within this region is a short arginine-rich motif found in a large class of RNA binding proteins. Substitution of multiple residues within the arginine-rich motif abolishes oligomerization, whereas several single-amino-acid substitution mutants oligomerize but do not bind RNA. Thus, Rev's arginine-rich motif participates in two distinct functions: oligomerization and RNA binding.
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PMID:Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein: a dual function for an arginine-rich binding motif. 171 76

Expression of human immunodeficiency virus type 1 structural proteins requires both the viral Rev trans-activator and its cis-acting RNA target sequence, the Rev response element (RRE). The RRE has been mapped to a conserved region of the HIV-1 env gene and is predicted to form a complex, highly stable RNA stem-loop structure. Site-directed mutagenesis was used to define a small subdomain of the RRE, termed stem-loop II, that is essential for biological activity. Gel retardation assays demonstrated that the Rev trans-activator is a sequence-specific RNA binding protein. The RRE stem-loop II subdomain was found to be both necessary and sufficient for the binding of Rev by the RRE. We propose that the HIV-1 Rev trans-activator belongs to a new class of sequence-specific RNA binding proteins characterized by the presence of an arginine-rich binding motif.
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PMID:HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence. 240 30

When the recognition sequence of a ribozyme is extended beyond a certain length, turnover is slowed and specificity is decreased. Here, it is shown that a protein can help a ribozyme overcome these general limitations on ribozyme activity. Cleavage of an RNA oligonucleotide by a hammerhead ribozyme is enhanced 10- to 20-fold upon addition of a protein derived from the p7 nucleocapsid (NC) protein of human immunodeficiency virus-type 1. The NC protein also enhances the ability of the ribozyme to discriminate between cleavage of RNA oligonucleotides with differing sequences. These catalytic improvements can be attributed to the strand exchange activity of this RNA binding protein. It is conceivable that endogenous or added proteins may provide analogous increases in ribozyme activity and specificity in vivo.
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PMID:Protein enhancement of hammerhead ribozyme catalysis. 769 97

The nucleocapsid protein NCp7, which is the major genomic RNA binding protein of human immunodeficiency virus type 1, plays an important role in several key steps of the viral life cycle. Many of the NCp7 activities, notably the nucleic acid annealing and the genomic RNA wrapping ones, are thought to be linked to a nonspecific binding of NCp7 to its nucleic acid targets. The mechanism of these activities is still debated but several clues are in favor of an intermediate aggregation of nucleic acids by NCp7. To check and characterize the nucleic acid aggregating properties of NCp7, we investigated the interaction of NCp7 with the model RNA homopolymer, polyA, by quasielastic light scattering and optical density measurements. The ordered growth of monodisperse large particles independently of the nucleic acid size and the almost complete covering of polyA by NCp7 strongly suggested an ordered aggregation mechanism. The aggregate kinetics of growth in the optimum protein concentration range (> or = 2 microM) were governed by a so-called Ostwald ripening mechanism limited by transfer of NCp7-covered polyA complexes from small to large aggregates. The aggregation process was strongly dependent on both Na+ and Mg2+ concentrations, the optimum concentrations being in the physiological range. Similar conclusions held true when polyA was replaced by 16S + 23S ribosomal RNA, suggesting that the NCp7 aggregating properties were only poorly dependent on the nucleic acid sequence and structure. Finally, as in the NCp7 annealing activities, the basic regions of NCp7, but not the zinc fingers, were found critical in nucleic acid aggregation. Taken together, our data indicate that NCp7 is a highly efficient nucleic acid aggregating agent and strengthen the hypothesis that aggregation may constitute a transient step in various NCp7 functions.
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PMID:Ordered aggregation of ribonucleic acids by the human immunodeficiency virus type 1 nucleocapsid protein. 905 95

We have cloned and characterized Xlrbpa, a double-stranded RNA-binding protein from Xenopus laevis. Xlrbpa is a protein of 33 kD and contains three tandemly arranged, double-stranded RNA-binding domains (dsRBDs) that bind exclusively to double-stranded RNA in vitro, but fail to bind either single-stranded RNA or DNA. Sequence data and the overall organization of the protein suggest that Xlrbpa is the Xenopus homologue of human TAR-RNA binding protein (TRBP), a protein isolated by its ability to bind to human immunodeficiency virus (HIV) TAR-RNA. In transfection assays, TRBP has also been shown to inhibit the interferon-induced protein kinase PKR possibly by direct physical interaction. To determine the function of Xlrbpa and its human homologue we studied the expression and intracellular distribution of the two proteins. Xlrbpa is ubiquitously expressed with marked quantitative differences amongst all tissues. Xlrbpa and human TRBP can be detected in the cytoplasm and nucleus by immunofluorescence staining and Western blotting. Sedimentation gradient analyses and immunoprecipitation experiments suggest an association of cytoplasmic Xlrbpa with ribosomes. In contrast, a control construct containing two dsRBDs fails to associate with ribosomes in microinjected Xenopus oocytes. Nuclear staining of Xenopus lampbrush chromosome preparations showed the association of the protein with nucleoli, again indicating an association of the protein with ribosomal RNAs. Additionally, Xlrbpa could be located on lampbrush chromosomes and in snurposomes. Immunoprecipitations of nuclear extracts demonstrated the presence of the protein in heterogeneous nuclear (hn) RNP particles, but not in small nuclear RNPs, explaining the chromosomal localization of the protein. It thus appears that Xlrbpa is a general double-stranded RNA-binding protein which is associated with the majority of cellular RNAs, ribosomal RNAs, and hnRNAs either alone or as part of an hnRNP complex.
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PMID:Xlrbpa, a double-stranded RNA-binding protein associated with ribosomes and heterogeneous nuclear RNPs. 923 68

Transcriptional regulation of the human immunodeficiency virus type 1 (HIV-1) genome is mediated by viral and cellular factors. TAR, an unusual RNA regulatory element with a stem-bulge-loop structure at the 5' ends of all nascent viral transcripts is critical for HIV-1 transcription. TAR is the target for Tat, a viral transcription factor encoded early in the HIV-1 life-cycle and essential for gene expression. Evidence demonstrating the interaction of a cellular ssDNA/RNA binding protein, YB-1, with TAR through a region which is important for Tat interaction is presented. Interestingly, results from protein-protein interaction studies revealed that YB-1 can also form a complex with Tat. Results from mapping experiments suggest that while the region spanning aa 125-203 within YB-1 is essential for its association with TAR, a truncated YB-1 spanning aa 1-125 can weakly bind to Tat. Functionally, overexpression of full-length YB-1 enhanced Tat-induced activation of the HIV-1 minimal promoter containing TAR sequences, whereas mutant YB- 1 with no ability to bind to Tat and TAR failed to affect Tat-mediated activation. Expression of mutant YB-1(1-125), which binds to Tat but not RNA, decreased Tat-mediated enhancement of virus transcription. These observations suggest that while full-length YB-1 may function as a facilitator and, by interaction with both Tat and TAR, increase the level of Tat:TAR association, mutant YB-1 with no TAR binding activity, by complexing with Tat, may prevent Tat interaction with TAR. The importance of these findings in light of the proposed mechanism of Tat function is discussed.
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PMID:Interaction of YB-1 with human immunodeficiency virus type 1 Tat and TAR RNA modulates viral promoter activity. 1057 56

RNA binding proteins often contain multiple arginine glycine repeats, a sequence that is frequently methylated by protein arginine methyltransferases. The role of this posttranslational modification in the life cycle of RNA binding proteins is not well understood. Herein, we report that Sam68, a heteronuclear ribonucleoprotein K homology domain containing RNA binding protein, associates with and is methylated in vivo by the protein arginine N-methyltransferase 1 (PRMT1). Sam68 contains asymmetrical dimethylarginines near its proline motif P3 as assessed by using a novel asymmetrical dimethylarginine-specific antibody and mass spectrometry. Deletion of the methylation sites and the use of methylase inhibitors resulted in Sam68 accumulation in the cytoplasm. Sam68 was also detected in the cytoplasm of PRMT1-deficient embryonic stem cells. Although the cellular function of Sam68 is unknown, it has been shown to export unspliced human immunodeficiency virus RNAs. Cells treated with methylase inhibitors prevented the ability of Sam68 to export unspliced human immunodeficiency virus RNAs. Other K homology domain RNA binding proteins, including SLM-1, SLM-2, QKI-5, GRP33, and heteronuclear ribonucleoprotein K were also methylated in vivo. These findings demonstrate that RNA binding proteins are in vivo substrates for PRMT1, and their methylation is essential for their proper localization and function.
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PMID:Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1. 1252 43

Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA binding protein and RNA-editing enzyme that modifies cellular and viral RNAs, including coding and noncoding RNAs. This interferon (IFN)-induced protein was expected to have an antiviral role, but recent studies have demonstrated that it promotes the replication of many RNA viruses. The data from these experiments show that ADAR1 directly enhances replication of hepatitis delta virus, human immunodeficiency virus type 1, vesicular stomatitis virus, and measles virus. The proviral activity of ADAR1 occurs through two mechanisms: RNA editing and inhibition of RNA-activated protein kinase (PKR). While these pathways have been found independently, the two mechanisms can act in concert to increase viral replication and contribute to viral pathogenesis. This novel type of proviral regulation by an IFN-induced protein, combined with some antiviral effects of hyperediting, sheds new light on the importance of ADAR1 during viral infection and transforms our overall understanding of the innate immune response.
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PMID:Enhancement of replication of RNA viruses by ADAR1 via RNA editing and inhibition of RNA-activated protein kinase. 2149 91

Human immunodeficiency virus (HIV) exploits cellular proteins during its replicative cycle and latent infection. The positive transcription elongation factor b (P-TEFb) is a key cellular transcription factor critical for these viral processes and is a drug target. During viral replication, P-TEFb is recruited via interactions of its cyclin T1 subunit with the HIV Tat (transactivator of transcription) protein and TAR (transactivation response) element. Through RNA silencing and over-expression experiments, we discovered that nuclear factor 90 (NF90), a cellular RNA binding protein, regulates P-TEFb expression. NF90 depletion reduced cyclin T1 protein levels by inhibiting translation initiation. Regulation was mediated by the 3' untranslated region of cyclin T1 mRNA independently of microRNAs. Cyclin T1 induction is involved in the escape of HIV-1 from latency. We show that the activation of viral replication by phorbol ester in latently infected monocytic cells requires the posttranscriptional induction of NF90 and cyclin T1, implicating NF90 in protein kinase C signaling pathways. This investigation reveals a novel mechanism of cyclin T1 regulation and establishes NF90 as a regulator of HIV-1 replication during both productive infection and induction from latency.
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PMID:HIV-1 replication and latency are regulated by translational control of cyclin T1. 2176 96

TAR-RNA binding protein (TRBP) is a multidomain human protein involved in micro-RNA (miRNA) biogenesis. TRBP is a component of both the Dicer complex, which processes precursor miRNAs, and the RNA-induced silencing complex-loading complex. In addition, TRBP is implicated in the human immunodeficiency virus replication cycle and interferon-protein kinase R activity. TRBP contains 3 double-stranded RNA binding domains the first two of which have been shown to interact with miRNA precursors. Here we present the backbone resonance assignments and secondary structure of residues 19-228 of human TRBP2.
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PMID:Backbone resonance assignments of the micro-RNA precursor binding region of human TRBP. 2287 87


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