Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutants of the Escherichia coli initiator tRNA (tRNA(fMet)) have been used to examine the role of the anticodon and discriminator base in in vivo aminoacylation of tRNAs by cysteinyl-tRNA synthetase. Substitution of the methionine anticodon CAU with the cysteine anticodon GCA was found to allow initiation of protein synthesis by the mutant tRNA from a complementary initiation codon in a reporter protein. Sequencing of the protein revealed that cysteine comprised about half of the amino acid at the N terminus. An additional mutation, converting the discriminator base of tRNA(GCAfMet) from A73 to the base present in tRNA(Cys) (U73), resulted in a 6-fold increase in the amount of protein produced and insertion of greater than or equal to 90% cysteine in response to the complementary initiation codon. Substitution of C73 or G73 at the discriminator position led to insertion of little or no cysteine, indicating the importance of U73 for recognition of the tRNA by cysteinyl-tRNA synthetase. Single base changes in the anticodon of tRNA(GCAfMet) containing U73 from GCA to UCA, GUA, GCC, and GCG (changes underlined) eliminated or dramatically reduced cysteine insertion by the mutant initiator tRNA indicating that all three cysteine anticodon bases are essential for specific aminoacylation of the tRNA with cysteine in vivo.
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PMID:The anticodon and discriminator base are major determinants of cysteine tRNA identity in vivo. 137 31

The role of the anticodon and discriminator base in aminoacylation of tRNAs with tryptophan has been explored using a recently developed in vivo assay based on initiation of protein synthesis by mischarged mutants of the Escherichia coli initiator tRNA. Substitution of the methionine anticodon CAU with the tryptophan anticodon CCA caused tRNA(fMet) to be aminoacylated with both methionine and tryptophan in vivo, as determined by analysis of the amino acids inserted by the mutant tRNA at the translational start site of a reporter protein containing a tryptophan initiation codon. Conversion of the discriminator base of tRNA(CCA)fMet from A73 to G73, the base present in tRNA(Trp), eliminated the in vivo methionine acceptor activity of the tRNA and resulted in complete charging with tryptophan. Single base changes in the anticodon of tRNA(CCA)fMet containing G73 from CCA to UCA, GCA, CAA, and CCG (changes underlined) essentially abolished tryptophan insertion, showing that all three anticodon bases specify the tryptophan identity of the tRNA. The important role of G73 in tryptophan identity was confirmed using mutants of an opal suppressor derivative of tRNA(Trp). Substitution of G73 with A73, C73, or U73 resulted in a large loss of the ability of the tRNA to suppress an opal stop codon in a reporter protein. Base pair substitutions at the first three positions of the acceptor stem of the suppressor tRNA caused 2-12-fold reductions in the efficiency of suppression without loss of specificity for aminoacylation of the tRNA with tryptophan.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conversion of a methionine initiator tRNA into a tryptophan-inserting elongator tRNA in vivo. 155 14

Recently, a close relation has been found between infection of the gastric mucosa by Campylobacter pylori and chronic gastritis. To establish the possible existence of characteristic morphologic changes in this disease, which can be differentiated from other unrelated forms of gastritis, we analyzed the antral biopsies obtained from 75 patients, 35 with duodenal peptic ulcer and 40 with nonulcerous dyspepsia. The diagnosis of C. pylori infection is based on positive biopsy culture or, if not, when following three requirements are met: positive urease test before 24 hours, identification of the germ by Gram stain and visualization in the tissue of microorganisms with morphology similar to that of C. pylori. We found that 85.5% of the 55 patients with C. pylori infection present active chronic gastritis with lymphoid nodes (GCA + NL), while this morphology is only found in 5 of the 20 uninfected patients. The association of GCA + NL with C. pylori infection is highly significant (p less than 0.0001). We think that it could be a local immunologic response to the stimulus of the bacterial antigen, and that it has sufficient morphologic entity to differentiate it from other inflammatory processes of the gastric mucosa of still unknown etiology.
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PMID:[Morphology of chronic gastritis associated with Campylobacter pylori infection]. 262 10

In this paper we describe the construction of a yeast tRNACys UGA suppressor. After specific hydrolysis of the parent molecule, the first base of the anticodon GCA was replaced by a uracil. The resulting molecule, harboring a UCA anticodon, was injected into Xenopus laevis oocytes in order to test its biological activities. The level of aminoacylation was similar to that of the parent molecule. Readthrough of the UGA termination codon in beta-globin mRNA, coinjected with the tRNA, indicated suppressor activity; however, tRNACys (anticodon UCA) was a much less efficient suppressor than others tested under the same conditions. We see no post-transcriptional modification of the uracil in the anticodon wobble position after injection into oocytes. This may be related to the low suppressor activity; however, it is also possible that other features of tRNACys structure may be unadapted to efficient UCA anticodon function.
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PMID:Construction of a UGA suppressor tRNA by modification in vitro of yeast tRNACys. 636 71

The CCA trinucleotide is a universally conserved feature of the 3' end of tRNAs, where it serves as the site of amino acid attachment. Despite this extreme conservation, we have isolated functional mutants of tRNA(His) and tRNA(Val1) with altered CCA ends. A mutant that leads to de-repression of the histidine biosynthetic operon in Salmonella typhimurium has been characterized and found to have the CCA end of the sole tRNA(His) species mutated to UCA. However, constructed mutants of tRNA(His) with ACA or GCA ends appeared to be nonfunctional in vivo. Mutants of Escherichia coli tRNA(Val1) with GCA or ACA ends were isolated on the basis of their ability to promote frameshifting at a specific sequence. These same tRNA(Val1) mutants also caused read-through of stop codons that were one, or in some instances two, codons downstream of the valine codon decoded by the mutant tRNA. A startling implication of these data is that disruption of interactions between the CCA end of the tRNA and the large ribosomal subunit promotes these aberrant codon-anticodon interactions on the small ribosomal subunit.
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PMID:Functional tRNAs with altered 3' ends. 768 77

Deviations from the universal genetic code have evolved independently several times in ciliated protozoa. Thus, in some species UAA and UAG are no longer used as termination codons, but are read as glutamine, whereas in the genus Euplotes , UGA is translated as cysteine. We have investigated the nature of the tRNACys isoacceptor responsible for decoding UGA in Euplotes cells. Southern hybridization analyses indicated that a single DNA molecule of 630 bp encoding tRNACys exists in the macronucleus of Euplotes octocarinatus . Cloning and sequencing of this fragment revealed that it contains only one copy of a tRNACys gene, which codes for a normal tRNACys with GCA anticodon. This is the first report of the characterization of a tRNA gene in any hypotrichous ciliate. It contains putative signals for initiation and termination of transcription by RNA polymerase III and can be transcribed efficiently in vitro in HeLa cell nuclear extract. Intensive studies on the DNA and tRNA level involving PCR analyses have not disclosed the existence of any tRNA Cys isoacceptor with UCA or ICA anticodons. Translation of the UGA codon by tRNA sub GCA sup Cys necessitates a G:A mispairing in the first anticodon position. We discuss a number of aspects which might contribute to the finding that a near-cognate tRNA isoacceptor efficiently translates the UGA stop codon.
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PMID:The hypotrichous ciliate Euplotes octocarinatus has only one type of tRNACys with GCA anticodon encoded on a single macronuclear DNA molecule. 975 21

Intron-encoded U17 RNA is a member of the H/ACA box class of small nucleolar RNAs (snoRNAs) involved in ribosomal RNA (rRNA) maturation. U17 snoRNA shows typical characteristics of guide RNAs, which specify sites of pseudouridylation on the precursor rRNA (pre-rRNA). However, in spite of the presence of H and ACA boxes and short regions complementary to the pre-rRNA, its secondary structure does not show any evident pseudouridylation pocket. Moreover, its length is larger than the typical one of snoRNAs and it shows a more complex secondary structure compared to the canonical hairpin-hinge-hairpin-tail architecture. Greater knowledge of eukaryotic U17 snoRNA structure is needed to understand its precise function. Comparative molecular studies of this snoRNA with different vertebrates is still limited to a few cases. With the aim of increasing our understanding of the U17 snoRNA secondary structure, we cloned the U17 snoRNA coding sequence from 10 additional vertebrate taxa. On the basis of structure homology derived from sequence comparison and thermodynamic prediction, we propose a vertebrate consensus secondary structure and novel conserved sequence boxes for U17 snoRNA. Host gene localization of U17 coding sequence and its ability to serve as a guide sequence for RNA/RNA interaction has been evolutionarily traced from fish to mammals. It is interesting to note that turtle U17 snoRNAs show a noncanonical ACA box, mainly consisting in the GCA box. Microinjections in X. laevis oocytes of in vitro synthesized turtle transcripts containing the U17 RNA sequence which have canonical ACA, wild-type GCA, and mutated CCA and UCA boxes resulted in efficient production of mature U17 snoRNA.
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PMID:Comparative structure analysis of vertebrate U17 small nucleolar RNA (snoRNA). 1182 10

Cysteine is ligated to tRNA(Cys) by cysteinyl-tRNA synthetase in most organisms. However, in methanogenic archaea lacking cysteinyl-tRNA synthetase, O-phosphoserine is ligated to tRNA(Cys) by O-phosphoseryl-tRNA synthetase (SepRS), and the phosphoseryl-tRNA(Cys) is converted to cysteinyl-tRNA(Cys). In this study, we determined the crystal structure of the SepRS tetramer in complex with tRNA(Cys) and O-phosphoserine at 2.6-A resolution. The catalytic domain of SepRS recognizes the negatively charged side chain of O-phosphoserine at a noncanonical site, using the dipole moment of a conserved alpha-helix. The unique C-terminal domain specifically recognizes the anticodon GCA of tRNA(Cys). On the basis of the structure, we engineered SepRS to recognize tRNA(Cys) mutants with the anticodons UCA and CUA and clarified the anticodon recognition mechanism by crystallography. The mutant SepRS-tRNA pairs may be useful for translational incorporation of O-phosphoserine into proteins in response to the stop codons UGA and UAG.
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PMID:Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea. 1735 29

We determined the complete chloroplast genome (cpDNA) of Ginkgo biloba (common name: ginkgo), the only relict of ginkgophytes from the Triassic Period. The cpDNA molecule of ginkgo is quadripartite and circular, with a length of 156,945 bp, which is 6,458 bp shorter than that of Cycas taitungensis. In ginkgo cpDNA, rpl23 becomes pseudo, only one copy of ycf2 is retained, and there are at least five editing sites. We propose that the retained ycf2 is a duplicate of the ancestral ycf2, and the ancestral one has been lost from the inverted repeat A (IR(A)). This loss event should have occurred and led to the contraction of IRs after ginkgos diverged from other gymnosperms. A novel cluster of three transfer RNA (tRNA) genes, trnY-AUA, trnC-ACA, and trnSeC-UCA, was predicted to be located between trnC-GCA and rpoB of the large single-copy region. Our phylogenetic analysis strongly suggests that the three predicted tRNA genes are duplicates of trnC-GCA. Interestingly, in ginkgo cpDNA, the loss of one ycf2 copy does not significantly elevate the synonymous rate (Ks) of the retained copy, which disagrees with the view of Perry and Wolfe (2002) that one of the two-copy genes is subjected to elevated Ks when its counterpart has been lost. We hypothesize that the loss of one ycf2 is likely recent, and therefore, the acquired Ks of the retained copy is low. Our data reveal that ginkgo possesses several unique features that contribute to our understanding of the cpDNA evolution in seed plants.
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PMID:The complete chloroplast genome of Ginkgo biloba reveals the mechanism of inverted repeat contraction. 2240 32

Understanding of codon usage bias of Fritillaria cirrhosa can provide theoretical basis for heterologous biosynthesis of F. cirrhosa alkaloids by genetic engineering technology. A total of 9 843 full length coding sequences (CDS) from the F. cirrhosa transcriptome data were used for the analysis of codon usage bias. The GC and GC3s contents, effective number of codons(ENC) and relative synonymous codon usage (RSCU) were calculated using the CodonW software. The results show that the codon usage bias value is low in the CDS of F. cirrhosa. A total of 15 codons, including UUG, CUU, AUU, GUU, UCA, CCU, CCA, ACU, ACA, GCA, UAU, CAU, AAU, AGA and GGA, were identified as optimal codons in F. cirrhosa. The optimal codons generally end with A/T at the third codon position. By the transcriptome annotation, we found 26 CDSs possibly involved in the biosynthesis of alkaloids in the F. cirrhosa. The proportion of rare codons of Escherichia coli and Saccharomyces cerevisiae are low in these CDSs. We also proposed a method for the codonoptimization in these target genes. Our work lays the foundation for further study on the biosynthesis of alkaloids of the F. cirrhosa in heterologous species.
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PMID:[Analysis of codon usage bias based on Fritillaria cirrhosa transcriptome]. 2890 Nov 1


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