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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After our first observation of codon context effects in missense suppression ( Murgola & Pagel , 1983), we measured the suppression of missense mutations at two positions in trpA in Escherichia coli. The suppressible codons in the trpA messenger RNA were the lysine codons, AAA and AAG, and the glutamic acid codons, GAA and GAG. The mRNA sites of the codons correspond to amino acids 211 and 234 of the trpA polypeptide, positions at which glycine is the wild-type amino acid. Our data demonstrated codon context effects with both pairs of codons. The results indicate that suppression of AAA and AAG by mutant lysine transfer RNAs was more efficient at 211 than at 234, whereas suppression of GAA and GAG by two different mutant glycine tRNAs was more efficient at 234 than at 211. In general, the context effects were more pronounced with GAG and AAG than with GAA and AAA. (In some instances it appeared that suppression of GAA or AAA at a given position was more effective than suppression of GAG or AAG.) By contrast, no context effects were observed with a glyT suppressor of AAA and AAG, a glyT GAA/G-suppressor, and a glyU suppressor of GAG. Our observation of this phenomenon in missense suppression demonstrates that codon context can affect polypeptide elongation and that the effects can be different depending on the codons and tRNAs examined. It is suggested that tRNA-tRNA interaction on the ribosome is involved in the observed context effects.
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PMID:Codon context effects in missense suppression. 637 55

The reading of glutamine and lysine codons during protein synthesis in vitro has been investigated using an MS2-RNA-programed system derived from Escherichia coli. Under conditions when either glutaminyl-tRNA1Gln (s2UUG) or glutaminyl-tRNA2Gln (CUG) was the only source of glutamine for protein synthesis both tRNAs were able to read the glutamine codons CAA and CAG as indicated by the incorporation of labeled glutamine into the pertinent coat protein tryptic peptides. On the other hand, when the two glutamine tRNAs competed for the codon CAA the reading efficiency of the anticodon s2UUG, which reads the codon according to the wobble rules, was almost 40 times higher than that of the competing anticodon CUG, which reads the codon by "two out of three," i.e. it cannot form a regular base pair with the third codon position. In reading the codon CAG the anticodon CUG was approximately eight times more efficient than the anticodon s2UUG. The lysyl-tRNA1Lys (CUU) could not alone sustain any detectable coat protein synthesis in the MS2 system indicating that there was no significant reading of the lysine codon AAA. This conclusion is supported by the outcome of experiments where lysyl-tRNA1Lys (CUU) and lysyl-tRNA2Lys (s2UUU) competed for the codon AAA. The reading efficiency of the anticodon CUU was less than 1% of that of the competing s2UUU which represents the limit of resolution of our experimental system. When the two lysine tRNAs competed for the codon AAG the anticodon CUU was about four times more efficient than s2UUU. These results are discussed in the context of the two out of three hypothesis, which attempts to relate the frequency of such reading to the hydrogen bonding properties of the codon nucleotides.
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PMID:Codon reading and translational error. Reading of the glutamine and lysine codons during protein synthesis in vitro. 678 93

Isoaccepting lysyl-tRNAs from virus-transformed cells in culture were fractionated in the RPC-5 system into peaks 1, 2, 4, 5a, 5, and 6. tRNALys6 previously was found predominantly associated with transformed cells. The codon response of each peak was determined in an E. coli ribosomal binding assay. tRNALys1, tRNALys2, and tRNALys4 are highly specific for the 5'AAG3' codon. tRNALys5 and tRNALys5a preferentially bind in response to AAA. tRNALys6 binds in response to AAA 3-fold better than in response to AAG. The presence of thiolated nucleosides in the anticodon regions of tRNALys5a, tRNALys5, and tRNALys6 is indicated by I2-inactivation of aminoacylation ability with no effect on the other is isoacceptors. Functional abilities of the isoacceptors were compared in a wheat germ translational system with tobacco mosaic virus RNA as messenger. All of the isoacceptors function about equally well in translation except for tRNALys6, which is only 14 to 24% as effective as the other isoacceptors.
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PMID:Codon binding and translational properties of an isoaccepting lysine tRNA peculiar to virus-transformed Cells. 680 26

Isoacceptors of rabbit liver tRNALys which preferentially translate the codon AAG were compared for their function in several aspects of translation. As shown in other laboratories, Lys-tRNALys1,2 are two isoacceptors which differ from each other by a single base pair and are fully modified with N6-threonyl-adenosine adjacent to the anticodon. Lys-tRNALys4, which occurs commonly in rapidly dividing mammalian cells and tissues, is hypomodified at several bases and contains a precursor of N6-threonyl-adenosine next to its anticodon. These isoacceptors were incubated in cell-free protein synthesizing systems which contain rabbit globin mRNA. (Lys-tRNALys3 which translates AAA was also included.) The resulting globin was isolated and digested with trypsin, and the relative incorporation of lysine from Lys-tRNALys1,2 and from Lys-tRNALys4 into lysine-containing sites in the globin peptides as determined. Lys-tRNALys1,2 and Lys-tRNALys4 translate AAG preferentially, but Lys-tRNALys4 wobbles more than the former and translates AAA codons more efficiently. Overall, Lys-tRNALys1,2 is preferred in globin synthesis by about 30% compared to Lys-tRNALys4, and with one exception, the incorporation of lysine into the individual AAG lysine-containing sites in globin occurs more efficiently from Lys-tRNALys1,2. There is, however, considerable variation from site to site in the relative efficiencies of the Lys-tRNAs in incorporation.
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PMID:The effects of a post-transcriptional modification on the function of tRNALys isoaccepting species in translation. 691 45

Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid adenomas and 7 toxic multinodular goiters) were analyzed. Genomic DNA was extracted from paraffin-embedded tissue sections, from which DNA fragments encoding the mutational hot spots of the receptor (the third cytoplasmic loop and the sixth transmembrane segment) were amplified by polymerase chain reaction. In the single-stranded conformation polymorphism (SSCP) analysis, only one hyperfunctioning adenoma (no. 21) displayed a migration abnormality. In sequence analysis, an unusual mutation of alternate three-base deletions at nucleotides 1953-1957 (AAA GAT ACC to AAG TCC), resulting in one amino acid deletion (Asp at 619) and one conservative amino acid substitution (Thr to Ser at 620), was identified in tumor DNA but not in leukocyte DNA of no. 21. Further, the normal sequence in these regions was confirmed in 10 randomly selected samples with normal migrating patterns in SSCP analysis. The functional property of the mutant with delta 619 and T620S (designated TSHR delta 619) was then evaluated with in vitro mutagenesis and transfection studies. Unexpectedly, however, there were no significant differences in TSH binding affinity, and basal and TSH-stimulated levels of cAMP and inositol 1,4,5-triphosphate between the TSHR delta 619 and the wt-TSHR. In conclusion, the incidence of the constitutively activating TSHR mutations in AFTNs appears to be low in Japan. The oncogenic potential of a novel somatic mutant TSHR delta 619 identified in a hyperfunctioning adenoma in this study is at present uncertain because of its intact function.
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PMID:Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan. 767 2

Two lysine isoacceptor tRNAs corresponding to the codons AAA and AAG, respectively, were isolated from squid (Loligo bleekeri), and their nucleotide sequences were determined. During this analysis, we discovered that the tRNA with the anticodon CUU was efficiently cleaved at a specific site in the presence of magnesium ions, whereas the tRNA with the anticodon UUU was not. Cleavage occurred almost exclusively at the phosphodiester linkage between G15 and D16 (p16). The most remarkable feature of this cleavage reaction is that the end product was not a 2',3'-cyclic phosphate but was mainly a 3'-phosphate. Thus, this reaction was distinct from the well characterized cleavage of yeast tRNA(Phe) by lead and from reactions catalyzed by various other metalloribozymes. The presence of a cytidine residue at position 60 was required for efficient cleavage but was not crucial for the reaction, and the entire tRNA molecule had to be intact for this specific and efficient cleavage reaction. The present study provides evidence that there exists a new catalytic mechanism for cleavage of tRNA that exploits biologically ubiquitous ions rather than toxic, nonessential ions such as lead.
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PMID:Highly specific and efficient cleavage of squid tRNA(Lys) catalyzed by magnesium ions. 773 Mar 14

Known types of pairings between mRNA bases and tRNA nucleosides are shown to be consistent with the notion of a translation space TS constructed such that certain wobble-pairings cannot be used in the same translation system without engendering confusion between keto-final codon twins like AAU(ASN)/AAG(LYS) and between amino-final codon twins like AAC(ASN)/AAA(LYS). When TS is abstractly formalized using Coxeter's face-first three-dimensional projection of a four-dimensional hypercube, the resulting model suggests a specific configurational logic for codon recognition by cognate tRNAs. Although this logic will in general permit codons and anticodons to form matching configurations whose loci are six lines parallel to the axis of a cylinder, confusion of keto-final and amino-final codon twins may result from wobble-pairings whose loci are the two of these lines off the surface of the cylinder.
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PMID:A geometric model for codon recognition logic. 805 66

Through sequencing of amplified DNA containing the appropriate alpha-globin genes we have identified the base substitution leading to the formation of Hb G-Philadelphia [alpha 68(E17)Asn Lys]. Three subjects (approximately 25% Hb G) had an ACC AAA change at codon 68 of the alpha 2-globin gene; the chromosome with this mutation carried two alpha genes (alpha alpha). Six subjects (approximately 33% Hb G) had an AAC AAG change at the same codon of the alpha 2 alpha 1 hybrid gene on a chromosome with the 3.7 kb deletion (-alpha 3.7). These results indicate two independent mutations which likely occurred in different populations; increase in the level of Hb G is primarily dependent upon the loss of one or more alpha-globin genes.
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PMID:Two different mutations in codon 68 are observed in Hb G-Philadelphia heterozygotes. 817 6

Streptomyces are bacteria with a very high chromosomal G+C composition (> 70 mol%) and extremely biased codon usage. In order to investigate the relationship between codon usage and gene expression in Streptomyces, we used ssi (Streptomyces subtilisin inhibitor) as a reporter gene and monitored its secretory expression in S. lividans. In consequence of alteration of the native codons of Leu, Lys and Ser of ssi to minor ones by site-directed mutagenesis, i.e., Leu79-Leu80: CTG-CTC to TTA-TTA, Lys89: AAG to AAA, Ser108-Ser109: TCG-AGC to TCT-TCT, respectively, the production of SSI was reduced remarkably in the case of TTA codons, while it was slightly increased in the case of AAA and almost the same in TCT codons. This conspicuous decrease found for Leu codon replacement was probably due to the low availability of intracellular tRNA(Leu) (UUA), a product of bldA which has been reported to be expressed only during the late stage of growth.
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PMID:Effect of a rare leucine codon, TTA, on expression of a foreign gene in Streptomyces lividans. 844 4

The blood clam Barbatia lima subsp. from Amami-Oshima, Japan, expresses three types of haemoglobins in erythrocytes: a tetramer (alpha 2 beta 2), a homodimer (delta 2) and a polymer consisting of two kinds of chains, a 34 kDa two-domain (2D) globin and a delta chain. This is in sharp contrast to the congeneric clams B. reeveana (a North American species) and B. lima from Kochi, Japan, each containing a tetramer and a polymer consisting of the 2D globin, but not the delta chain. We have determined the cDNA-derived amino acid sequences of all four chains, alpha (163 residues), beta (155 residues), delta (152 residues) and 2D (308 residues) of B. lima (Amami-Oshima). The alpha chain has an extremely long N-terminal extension of 20 residues that may form a 'pre-A helix', and this makes the alpha chain the longest known globin. B. lima alpha and beta chains show about 50% sequence identity with the alpha and beta chains, respectively, of tetrameric haemoglobin from a related clam, Anadara trapezia. The B. lima homodimeric delta chain shows 71-74% identity with each of the two domains of the 2D chain, but only 39% identity with the homodimeric gamma chain of Anadara. In addition, the alignment of amino acid sequences of the delta chain and the two domains of the 2D chain revealed that the delta chain lacks one amino acid (Lys) at the C-terminus, suggesting that the C-terminal Lys (codon AAA or AAG) of the two domains of 2D chain could result from the stop codon TAA in the delta chain by nucleotide substitutions. These results, together with the fact that the delta and 2D chains form a polymeric haemoglobin, indicates that the delta chain is the ancestral single-domain globin for the 2D globin. The delta chain is expressed only in B. lima (Amami-Oshima), and appears to be a relic of molecular evolution.
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PMID:Two-domain haemoglobin of the blood clam Barbatia lima resulted from the recent gene duplication of the single-domain delta chain. 857 93


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