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At least 1,261 records · Page 70Linked to original sources
PubMed2001

A role for initiation codon context in chloroplast translation.

To study the role of initiation codon context in chloroplast protein synthesis, we mutated the three nucleotides immediately upstream of the initiation codon (the -1 triplet) of two chloroplast genes in the alga Chlamydomonas reinhardtii. In prokaryotes, the -1 triplet has been proposed to base pair with either the 530 loop of 16S rRNA or the extended anticodon of fMet-tRNA. We found that in vivo, none of the chloroplast mutations affected mRNA stability. However, certain mutations did cause a temperature-sensitive decrease in translation and a more dramatic decrease at room temperature when combined with an AUU initiation codon. These mutations disrupt the proposed extended base pairing interaction with the fMet-tRNA anticodon loop, suggesting that this interaction may be important in vivo. Mutations that would still permit base pairing with the 530 loop of the 16S rRNA also had a negative effect on translation, suggesting that this interaction does not occur in vivo. Extended base pairing surrounding the initiation codon may be part of a mechanism to compensate for the lack of a classic Shine-Dalgarno rRNA interaction in the translation of some chloroplast mRNAs.

Animals↗
PubMed1999

Combinatorial codons: a computer program to approximate amino acid probabilities with biased nucleotide usage.

Using techniques from optimization theory, we have developed a computer program that approximates a desired probability distribution for amino acids by imposing a probability distribution on the four nucleotides in each of the three codon positions. These base probabilities allow for the generation of biased codons for use in mutational studies and in the design of biologically encoded libraries. The dependencies between codons in the genetic code often makes the exact generation of the desired probability distribution for amino acids impossible. Compromises are often necessary. The program, therefore, not only solves for the "optimal" approximation to the desired distribution (where the definition of "optimal" is influenced by several types of parameters entered by the user), but also solves for a number of "sub-optimal" solutions that are classified into families of similar solutions. A representative of each family is presented to the program user, who can then choose the type of approximation that is best for the intended application. The Combinatorial Codons program is available for use over the web from http://www.wi.mit.edu/kim/computing.html.

Amino Acids↗
PubMed1999

TTG as the initiation codon of Salmonella slyA, a gene required for survival within macrophages.

The slyA gene, which has been implicated in the virulence of Salmonella serovar Typhimurium and its survival in macrophages, is widely distributed among different Salmonella serovars. In this study, we cloned and sequenced the translational initiation region of the slyA gene from nine different serovars and found sequence differences in the previously proposed ATG initiation codon but not in a TTG triplet, another putative initiation codon in the slyA gene. Therefore, we determined the actual translational initiation site of the slyA gene by analyzing slyA genes with defined mutation in either the ATG or TTG sequences in an in vitro translation assay and a quantitative hemolytic assay in Escherichia coli. The replacement of TTG by TTC in the slyA gene significantly reduced both the amount of protein synthesized and the hemolytic activity of a transformed strain of E. coli, while replacement of ATG by ATC had no effect in these assays. In addition, the amino acid sequence analysis of the His-tagged SlyA protein showed that it was identical with the amino acid sequence deduced from the 5' end of the slyA gene with a TTG initiation codon. Our results suggest that TTG serves as the translational initiation codon for the slyA gene of Salmonella.

Amino Acid Sequence↗
PubMed2006

Human alpha2-globin nonsense-mediated mRNA decay induced by a novel alpha-thalassaemia frameshift mutation at codon 22.

We describe a novel alpha-thalassaemia determinant in a 3-year-old girl presenting a mild microcytic and hypochromic anaemia, and normal haemoglobin A2 level. Molecular studies revealed heterozygosity for a novel microdeletion (-C) at codon 22 of the alpha2-globin gene. As the frameshift mutation generates a premature translation termination codon at position 48/49, we investigated the effect of the nonsense codon on the alpha2-globin gene expression. Although it does not affect RNA splicing, the premature nonsense codon induces accelerated mRNA degradation. To our knowledge, this is the first time the nonsense-mediated mRNA decay has been reported to occur in human alpha-globin mRNA.

Codon, Nonsense↗
PubMed1994

Gene screening in Japanese families with complete deficiency of thyroxine-binding globulin demonstrates that a nucleotide deletion at codon 352 may be a race specific mutation.

OBJECTIVE: Thyroxine-binding globulin (TBG) is a serum protein that transports 75% of circulating thyroxine. Eleven naturally occurring mutations in the human TBG gene have been identified, ten of which alter the properties of the molecule. Three of these mutations produce complete deficiency of TBG (TBG-CD) and four are associated with a second mutation in codon 283 (TBG-poly) which is polymorphic in some ethnic groups but, when present alone, does not alter the properties of the TBG molecule. In this communication we investigate whether two unrelated Japanese families with TBG-CD harboured the TBG-CDJ mutation in codon 352 associated with TBG-CD in families residing in more distant locations of the Japanese Islands. In addition we examined the possible association with TBG-poly and its incidence in the Japanese population. DESIGN: Mutant alleles were identified by amplification of genomic DNAs by the polymerase chain reaction, using allele-specific oligonucleotide primers. PATIENTS: Eight family members and 25 normal subjects. MEASUREMENTS: Serum free thyroxine and TBG concentration were measured by a conventional radioimmunoassay and a more sensitive enzyme immunoassay. Genomic DNAs were extracted from white blood cells and specific mutations at codons 352 and 283 were identified by allele-specific amplification. RESULTS: Three males and three females, whose serum TBG levels were decreased, had mutations at codon 352 as hemizygous and heterozygous, respectively. This mutation was not present in the DNA of any of the related or unrelated subjects with normal TBG concentration. The presence of TBG-poly was demonstrated in only one heterozygous family member and in six out of 30 alleles (20%) in normal unrelated subjects. The frequency of this TBG polymorphism in the Japanese is similar to that of 16% reported in French Canadians. CONCLUSIONS: We conclude that TBG-CDJ might be a prevalent cause of complete deficiency of thyroxine-binding globulin in the Japanese and that TBG-poly probably appeared before the divergence of human races.

Alleles↗
PubMed1993

Codon preference of Aedes aegypti and Aedes albopictus.

The codon bias of two Aedes mosquito species was examined using a sign test. In general, there appeared to be some preference for C + G at the third base position, although this was not statistically significant. While amino acids such as phenylalanine and tyrosine clearly displayed biases, others such as valine and serine appeared to have little or no bias for any particular codon. Three homologous genes of Aedes aegypti and Drosophila melanogaster were compared using the chi-square test and the codon bias of the two species compared. Drosophila melanogaster was found to have a much stronger bias for C + G at the third base position compared to Aedes. The implications and usefulness of the codon bias are discussed.

Aedes↗
PubMed1996

mRNA sequences influencing translation and the selection of AUG initiator codons in the yeast Saccharomyces cerevisiae.

The secondary structure and sequences influencing the expression and selection of the AUG initiator codon in the yeast Saccharomyces cerevisiae were investigated with two fused genes, which were composed of either the CYC7 or CYC1 leader regions, respectively, linked to the lacZ coding region. In addition, the strains contained the upf1-delta disruption, which stabilized mRNAs that had premature termination codons, resulting in wild-type levels. The following major conclusions were reached by measuring beta-galactosidase activities in yeast strains having integrated single copies of the fused genes with various alterations in the 89 and 38 nucleotide-long untranslated CYC7 and CYC1 leader regions, respectively. The leader region adjacent to the AUG initiator codon was dispensable, but the nucleotide preceding the AUG initiator at position -3 modified the efficiency of translation by less than twofold, exhibiting an order of preference A > G > C > U. Upstream out-of-frame AUG triplets diminished initiation at the normal site, from essentially complete inhibition to approximately 50% inhibition, depending on the position of the upstream AUG triplet and on the context (-3 position nucleotides) of the two AUG triplets. In this regard, complete inhibition occurred when the upstream and downstream AUG triplets were closer together, and when the upstream and downstream AUG triplets had, respectively, optimal and suboptimal contexts. Thus, leaky scanning occurs in yeast, similar to its occurrence in higher eukaryotes. In contrast, termination codons between two AUG triplets causes reinitiation at the downstream AUG in higher eukaryotes, but not generally in yeast. Our results and the results of others with GCN4 mRNA and its derivatives indicate that reinitiation is not a general phenomenon in yeast, and that special sequences are required.

Base Sequence↗
PubMed2006

Translation initiation with GUC codon in the archaeon Halobacterium salinarum: implications for translation of leaderless mRNA and strict correlation between translation initiation and presence of mRNA.

We have investigated whether anticodon sequence mutant of an archaeal initiator tRNA can initiate protein synthesis using reporter genes carrying mutations in the initiation codon. Halobacterium salinarum was used as the model organism and the bacterio-opsin gene (bop), which encodes the precursor of the protein component of the purple membrane protein bacterio-opsin (Bop), was chosen as the reporter. We demonstrate that a CAU to GAC anticodon sequence mutant of Haloferax volcanii initiator tRNA can initiate Bop protein synthesis using GUC as the initiation codon in H. salinarum. We generated four mutant bop genes, each carrying the AUG to GUC initiation codon mutation, with or without a compensatory mutation to maintain a predicted stem-loop structure at the 5'-end of the bop mRNA, and with or without mutations to test translation initiation at a site corresponding to the amino terminus of mature bacterio-opsin. H. salinarum chromosomal recombinants containing these mutant genes were phenotypically Pum- (purple membrane negative). Upon transformation with a plasmid carrying the mutant initiator tRNA gene, only strains designed to maintain the bop mRNA stem-loop structure produced Bop and were phenotypically Pum+ as indicated by purple colony colour, and immunoblotting and spectral analysis of cell extracts. Thus GUC can serve as an initiation codon in archaea and the stem-loop structure in the bop mRNA is important for translation. Interestingly, for the same mutant mRNA, only transformants that produce Bop protein contain bop mRNA. These results suggest either a strong coupling between translation and mRNA stability or strong transcriptional polarity in H. salinarum.

5' Untranslated Regions↗
PubMed2007

Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli.

Certain C-terminal sequences of nascent peptide cause an efficient protein tagging by tmRNA system at stop codons in Escherichia coli. Here, we demonstrate that both mRNA cleavage and tmRNA tagging occur at UAG stop codon recognized specifically by polypeptide release factor 1 (RF-1) when the activity of RF-1 is reduced by a mutation in the prfA gene without requirement of particular C-terminal sequences of nascent peptide. The tmRNA tagging and mRNA cleavage in the prfA mutant were eliminated when the wild-type RF-1 but not RF-2 was supplied from plasmid. In addition, depletion of either RF-1 or RF-2 induces endonucleolytic cleavage and tmRNA tagging at UAG or UGA stop codons respectively. We conclude that ribosome stalling at the cognate stop codon caused by reduced activity or expression of RF-1 or RF-2 is responsible for mRNA cleavage. The present data along with our previous studies strongly suggest that ribosome stalling leads to endonucleolytic cleavage of mRNA in general resulting in non-stop mRNA and that the 3' end of non-stop mRNA is probably only target for the tmRNA system.

Codon, Terminator↗
PubMed1997

Mutation of RET codon 768 is associated with the FMTC phenotype.

Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are inherited cancer syndromes resulting from mutations in the RET proto-oncogene. Missense mutations of five codons in exons 10 and 11 are found in both MEN 2A and FMTC families, while mutations at codon 768 in exon 13 have been identified in three FMTC families. We report here the results of mutation analysis on a large multi-generation family with multiple cases of medullary thyroid carcinoma (MTC) or C-cell hyperplasia and two individuals with isolated adrenal medullary hyperplasia. A mutation in exon 13, which alters codon 768 from a GAG (Glu) to a GAC (Asp), was found to segregate with the FMTC phenotype in this family but not with the adrenal medullary hyperplasia. These findings suggest that the codon 768 mutation does not predispose to adrenal medullary hyperplasia, but is an accurate predictor of the MTC phenotype in this family.

Carcinoma, Medullary↗
PubMed1979

Chemical evidence for a codon-induced allosteric change in tRNALys involving the 7-methylguanosine residue 46.

[32P]TRNALys, from Escherichia coli, was modified with kethoxal, in the presence and absence of the oligonucleotide codon (A)4. The presence of the codon resulted in a faster modification rate of the tRNA at three guanine sites which were identified by a diagonal fingerprint method. A large increase in the modification rate occurred at the 7-methylguanosine residue 46 (m7G-46) in the presence of the codon: weakly enhanced modification was observed at G-15 and G-57. It is concluded that the formation of a codon-anticodon complex induces, primarily, a conformational change involving disruption of the m7G-46 from the m7G-46 . G-22 . C-13 base triple. Subsequently, the guanines of G-15 and G-57, in the D and T loops, respectively, become slightly more reactive, suggesting a weak tendency for these two interacting arms to unfold. The results are interpreted in terms of an equilibrium between two main conformers, and a third minor one; the possible significance of these conformers in protein biosynthesis, is considered.

Base Sequence↗
PubMed1980

Nucleotide sequence of simian virus 40 DNA: structure of the middle segment of the HindII + III restriction fragment B (sixth part of the T antigen gene) and codon usage.

We report here the nucleotide sequence of the simian virus 40 DNA region that lies between the EcoRII restriction endonuclease cleavage sites at map positions 0.214 and 0.281. The sequence was determined by partial chemical degradation of terminally labeled DNA fragments according to the procedure of Maxam and Gilbert. This region represents 6.7% of the SV40 genome and is located in the middle of HindII + III restriction fragment B. It is expressed as part of the early 19-S messenger RNA, which codes for the large-T antigen protein. Only one open reading frame for translation can be deduced from the message strand of the DNA and this reading frame connects in phase with the one of both neighboring fragments. This publication is the last in a series of papers about the T-antigen gene, and several properties of this gene and its product are discussed. The non-randomness of codon usage is similar to that previously discussed for the late part of the genome. Moreover, it appears that the choice of a third letter can be determined by the nature of the following codon; some codons which start with a pyrimidine are almost never preceded by an adenosine and some ANN-type codons are almost never preceded by a guanosine.

Amino Acid Sequence↗
PubMed2005

Effect of p53 codon 72 polymorphism on p53 protein expression in pterygium.

BACKGROUND: The p53 protein is expressed in pterygial epithelium, but the reported prevalence of its expression varies widely. Although the cause of this variation is unknown, several factors that may play a role have been investigated, but without conclusive findings. In the present study, the role of p53 codon 72 polymorphism, and that of both age and gender, on p53 expression in pterygium was investigated. METHODS: Pterygium and blood samples were harvested from 55 patients undergoing pterygium surgery. The pterygial specimens were studied immunohistochemically using antibodies against p53 protein. Polymerase chain reaction based analysis was used to resolve the p53 codon 72 polymorphism. RESULTS: Thirty-one (56.4%) of the 55 pterygial specimens were positive for p53 staining. The distributions of the three genotypes of the p53 codon 72 polymorphism in the p53-positive and -negative staining groups were not statistically different. The allelic frequency in the two groups was also not statistically different, nor was there any significant difference between both groups with respect to age or gender. CONCLUSIONS: A correlation between p53 codon 72 polymorphism, sex and gender and p53 protein expression was not found.

Age Factors↗
PubMed2005

The TGF-beta 1 gene codon 10 polymorphism contributes to the genetic predisposition to nephropathy in Type 1 diabetes.

AIMS: We hypothesize that transforming growth factor-beta (TGF-beta), a multifunctional growth factor which plays a key role in the development of tissue fibrosis, may be involved in the pathophysiology of diabetic nephropathy. Our aim was to examine three polymorphisms within the TGF-beta 1 gene, in codons 10, 25 and 263, for association with nephropathy in Type 1 diabetes. METHODS: We conducted a large case-control study using cases with Type 1 diabetes and clinical nephropathy. Controls were Type 1 diabetic subjects who have been injecting insulin for at least 50 years and have extremely low risk of nephropathy. Genotyping was by polymerase chain reaction with sequence-specific primers. RESULTS: There was a significant difference in the frequency of the TGF-beta 1 codon 10 genotypes in the diabetic nephropathy group (n = 420) when compared with the controls (n = 410, P = 0.007). There were no significant differences when the frequencies of the TGF-beta1 codons 25 and 263 genotypes in the diabetic nephropathy group were compared with the control group. CONCLUSIONS: In our study the TGF-beta 1 codon 10 polymorphism is associated with nephropathy in Type 1 diabetes and variation in this gene may contribute to the genetic predisposition to this complication in Type 1 diabetes.

Adult↗
PubMed2007

Transforming growth factor-beta1 polymorphisms in patients with brucellosis: an association between codon 10 and 25 polymorphisms and brucellosis.

This study examined the association between transforming growth factor (TGF)-beta1 polymorphisms and brucellosis. The TGF-beta1 genotypes at codons 10 and 25 were determined by an amplification refractory mutation system-PCR among 425 brucellosis patients and 213 healthy volunteers. The frequencies of TGF-beta1 codons 10 C and 25 G were significantly higher among patients than among controls, as was that of TGF-beta1 codon 10 C/C. The high-producer haplotype (CG/TG) was more frequent among patients than among controls. The findings suggest that genetic polymorphism in codons 10 and 25 of the TGF-beta1 gene might contribute to the development of brucellosis.

Brucellosis↗
PubMed1991

Lack of evidence of Ki-ras codon 12 mutations in melanocytic lesions.

A number of studies have failed to detect point mutations at codon 12 in the Ki-ras gene in melanocytic neoplasms. One recent study, however, has found a high percentage of Ki-ras codon 12 point mutations. In an effort to resolve this difference, the present study examined noncultured melanocytic lesions (i.e., 5 benign nevi, 10 dysplastic nevi, and 8 primary melanomas: 4 in situ and 4 invasive) for point mutations at codon 12 in the first exon of the Ki-ras proto-oncogene using polymerase chain reaction methodology with oligonucleotide hybridization and direct DNA sequencing. The results of this study indicates no detectable mutations in the 12th codon of the first exon of the Ki-ras gene in any premalignant or malignant melanocytic lesion examined.

Base Sequence↗
PubMed2003

Selective charging of tRNA isoacceptors explains patterns of codon usage.

We modeled how the charged levels of different transfer RNAs (tRNAs) that carry the same amino acid (isoacceptors) respond when this amino acid becomes growth-limiting. The charged levels will approach zero for some isoacceptors (such as tRNA2Leu) and remain high for others (such as tRNA4Leu), as determined by the concentrations of isoacceptors and how often their codons occur in protein synthesis. The theory accounts for (synonymous) codons for the same amino acid that are used in ribosome-mediated transcriptional attenuation, the choices of synonymous codons in trans-translating transfermessenger RNA, and the overrepresentation of rare codons in messenger RNAs for amino acid biosynthetic enzymes.

Amino Acids↗
PubMed1981

Suppressible four-base glycine and proline codons in yeast.

Five ICR-170--induced mutations at the His4 locus in yeast are +1 G.C (G, guanine; C, cytosine) additions in DNA regions that contain multiple G.C base pairs. These mutations represents both nonsuppressible and suppressible alleles. All externally, suppressible frameshift mutations occur in glycine and proline codons to produce the four-base codons GGGU (U, uracil), GGGG, and CCCU. This implies that suppression of these four-base codons in yeast, as in bacteria, involves a four-base anticodon or its functional equivalent. Two identical four-base codons (CCCU) at widely separate regions with His4 are not suppressed equally.

Base Sequence↗