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At least 1,621 records · Page 90Linked to original sources
PubMed1997

Preferential codon usage and two types of repetitive motifs in the fibroin gene of the Chinese oak silkworm, Antheraea pernyi.

In this paper we describe the peculiar structures and preferential codon usage found in wild silkworm fibroin genes. We determined a 1350 bp nucleotide sequence from the Chinese oak silkworm, Antheraea pernyi. The deduced amino acid sequence was partitioned into thirteen polyalanine-containing repetitive motifs, which was one of the characteristics of Antheraea fibroins. Eleven of these arrays can be classified into two types of motifs depending on difference in amino acid sequences following polyalanine. Repetitive motifs structurally similar to those of A. pernyi were detected in a homologue of the Japanese oak silkworm, Antheraea yamamai. The most remarkable feature of this study was preferential codon usage, especially seen in alanine synonymous codons within both homologues of Antheraea: isocodon GCA most frequently occurred in alanine isocodons. In contrast, GCU isocodon was the most abundant in Bombyx mori fibroin heavy chain that lacks polyalanine arrays. This result strongly suggests different modes of selective constraint between the two types of fibroin gene. The similar finding that GCA isocodon was most frequent in two dragline silk sequences of the spider, Nephila clavipes, is consistent with our results because of the repetitive polyalanine-containing arrays seen in spider dragline silk.

Amino Acid Sequence↗
PubMed1999

Translation initiation factor 3 antagonizes authentic start codon selection on leaderless mRNAs.

In this study, we have examined the influence of initiation factors on translation initiation of leaderless mRNAs whose 5'-terminal residues are the A of the AUG initiating codon. A 1:1 ratio of initiation factors to ribosomes abolished ternary complex formation at the authentic start codon of different leaderless mRNAs. Supporting this observation, in vitro translation assays using limiting ribosome concentrations with competing leaderless lambda cl and Escherichia coli ompA mRNAs, the latter containing a canonical ribosome binding site, revealed reduced cl synthesis relative to OmpA in the presence of added initiation factors. Using in vitro toeprinting and in vitro translation assays, we show that this effect can be attributed to IF3. Moreover, in vivo studies revealed that the translational efficiency of a leaderless reporter gene is decreased with increased IF3 levels. These studies are corroborated by the observed increased translational efficiency of a leaderless reporter construct in an infC mutant strain unable to discriminate against non-standard start codons. These results suggest that, in the absence of a leader or a Shine-Dalgarno sequence, the function(s) of IF3 limits stable 30S ternary complex formation.

5' Untranslated Regions↗
PubMed1999

Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp.

Several species of the genus Candida decode the standard leucine CUG codon as serine. This and other deviations from the standard genetic code in both nuclear and mitochondrial genomes invalidate the notion that the genetic code is frozen and universal and prompt the questions 'why alternative genetic codes evolved and, more importantly, how can an organism survive a genetic code change?' To address these two questions, we have attempted to reconstruct the early stages of Candida albicans CUG reassignment in the closely related yeast Saccharomyces cerevisiae. These studies suggest that this genetic code change was driven by selection using a molecular mechanism that requires CUG ambiguity. Such codon ambiguity induced a significant decrease in fitness, indicating that CUG reassignment can only be selected if it introduces an evolutionary edge to counteract the negative impact of ambiguity. We have shown that CUG ambiguity induces the expression of a novel set of stress proteins and triggers the general stress response, which, in turn, creates a competitive edge under stress conditions. In addition, CUG ambiguity in S. cerevisiae induces the expression of a number of novel phenotypes that mimic the natural resistance to stress characteristic of C. albicans. The identification of an evolutionary advantage created by CUG ambiguity is the first experimental evidence for a genetic code change driven by selection and suggests a novel role for codon reassignment in the adaptation to new ecological niches.

Adaptation, Biological↗
PubMed2002

Translational readthrough of the PDE2 stop codon modulates cAMP levels in Saccharomyces cerevisiae.

The efficiency of translation termination in yeast can vary several 100-fold, depending on the context around the stop codon. We performed a computer analysis designed to identify yeast open reading frames (ORFs) containing a readthrough motif surrounding the termination codon. Eight ORFs were found to display inefficient stop codon recognition, one of which, PDE2, encodes the high-affinity cAMP phosphodiesterase. We demonstrate that Pde2p stability is very impaired by the readthrough-dependent extension of the protein. A 20-fold increase in readthrough of PDE2 was observed in a [PSI+] as compared with a [psi-] strain. Consistent with this observation, an important increase in cAMP concentration was observed in suppressor backgrounds. These results provide a molecular explanation for at least some of the secondary phenotypes associated with suppressor backgrounds.

Codon, Terminator↗
PubMed2002

Expression of the Escherichia coli pcnB gene is translationally limited using an inefficient start codon: a second chromosomal example of translation initiated at AUU.

Expression of the gene pcnB, encoding the dispensable Escherichia coli poly(A) polymerase (PAPI), which is toxic when overproduced, was investigated. Its promoter was identified and found to be moderately strong when used to express a beta-galactosidase reporter. Expression levels were not affected by increasing or decreasing PcnB concentration. Translation of pcnB was found to initiate from the non-canonical initiation codon AUU. The only other coli gene reported to use AUU as initiation codon is infC, which encodes the initiation factor IF-3. AUU, in common with other rarely used initiation codons, is discriminated against by IF-3, resulting in the aborting of most AUU-promoted initiation events. This enables AUU to form part of an autoregulatory circuit controlling IF-3 production. We show that InfC discrimination reduces PcnB production fivefold. This is the first instance of this mechanism being used to limit severely the production of a potentially toxic product.

Base Sequence↗
PubMed2003

Stop codon recognition and interactions with peptide release factor RF3 of truncated and chimeric RF1 and RF2 from Escherichia coli.

Release factors RF1 and RF2 recognize stop codons present at the A-site of the ribosome and activate hydrolysis of peptidyl-tRNA to release the peptide chain. Interactions with RF3, a ribosome-dependent GTPase, then initiate a series of reactions that accelerate the dissociation of RF1 or RF2 and their recycling between ribosomes. Two regions of Escherichia coli RF1 and RF2 were identified previously as involved in stop codon recognition and peptidyl-tRNA hydrolysis. We show here that removing the N-terminal domain of RF1 or RF2 or exchanging this domain between the two factors does not affect RF specificity but has different effects on the activity of RF1 and RF2: truncated RF1 remains highly active and able to support rapid cell growth, whereas cells with truncated RF2 grow only poorly. Transplanting a loop of 13 amino acid residues from RF2 to RF1 switches the stop codon specificity. The interaction of the truncated factors with RF3 on the ribosome is defective: they fail to stimulate guanine nucleotide exchange on RF3, recycling is not stimulated by RF3, and nucleotide-free RF3 fails to stabilize the binding of RF1 or RF2 to the ribosome. However, the N-terminal domain seems not to be required for the expulsion of RF1 or RF2 by RF3:GTP.

Amino Acid Sequence↗
PubMed2000

Premature termination codons destabilize ferredoxin-1 mRNA when ferredoxin-1 is translated.

Ferredoxin-1 (Fed-1) mRNA is poorly translated in dark-treated tobacco (Nicotiana tabacum) leaves, resulting in destabilization of Fed-1 mRNA and a differential light/dark accumulation of the mRNA. Insertion of nonsense codons within the Fed-1 coding sequence disrupts the light regulation of Fed-1 mRNA abundance. Here we show that the nonsense codon effect results primarily from lowering the Fed-1 mRNA stability in light-treated leaf tissue and in rapidly growing tobacco cell cultures, but not in dark-treated leaf tissue. These results suggest that nonsense codons trigger a decay pathway distinct from that seen for Fed-1 mRNA in the dark. We propose that nonsense-mediated decay of nonsense-containing Fed-1 mRNA occurs in light-treated leaves and in non-photosynthetic tobacco culture cells where Fed-1 mRNA is being actively translated.

Cells, Cultured↗
PubMed2001

The polypeptide chain release factor eRF1 specifically contacts the s(4)UGA stop codon located in the A site of eukaryotic ribosomes.

It has been shown previously [Brown, C.M. & Tate, W.P. (1994) J. Biol. Chem. 269, 33164-33170.] that the polypeptide chain release factor RF2 involved in translation termination in prokaryotes was able to photocrossreact with mini-messenger RNAs containing stop signals in which U was replaced by 4-thiouridine (s4U). Here, using the same strategy we have monitored photocrosslinking to eukaryotic ribosomal components of 14-mer mRNA in the presence of tRNA(f)(Met), and 42-mer mRNA in the presence of tRNA(Asp) (tRNA(Asp) gene transcript). We show that: (a) both 14-mer and 42-mer mRNAs crossreact with ribosomal RNA and ribosomal proteins. The patterns of the crosslinked ribosomal proteins are similar with both mRNAs and sensitive to ionic conditions; (b) the crosslinking patterns obtained with 42-mer mRNAs show characteristic modification upon addition of tRNA(Asp) providing evidence for appropriate mRNA phasing onto the ribosome. Similar changes are not detected with the 14-mer mRNA.tRNA(f)(Met) pairs; (c) when eukaryotic polypeptide chain release factor 1 (eRF1) is added to the ribosome.tRNA(Asp) complex it crossreacts with the 42-mer mRNA containing the s(4)UGA stop codon located in the A site, but not with the s(4)UCA sense codon; this crosslink involves the N-terminal and middle domains of eRF1 but not the C domain which interacts with eukaryotic polypeptide chain release factor 3 (eRF3); (d) addition of eRF3 has no effect on the yield of eRF1-42-mer mRNA crosslinking and eRF3 does not crossreact with 42-mer mRNA. These experiments delineate the in vitro conditions allowing optimal phasing of mRNA on the eukaryotic ribosome and demonstrate a direct and specific contact of 'core' eRF1 and s(4)UGA stop codon within the ribosomal A site.

Animals↗
PubMed2001

Association of the vitamin D receptor gene start codon Fok I polymorphism with calcium oxalate stone disease.

OBJECTIVE: To assess the use of Fok I polymorphism (the most frequent polymorphism, at the start codon of the vitamin D receptor gene, VDR) as a convenient genetic marker in identifying the cause of urolithiasis. PATIENTS, SUBJECTS AND METHODS: A normal control group of 90 healthy subjects and 146 patients with calcium oxalate stones were examined. Using polymerase chain reaction (PCR)-based restriction analysis, the relationship between Fok I polymorphism and urolithiasis was evaluated. An unexcisable length of 265 bp was identified (allele CC) and two fragments (169 bp and 96 bp) identified as excisable lengths (allele TT). RESULTS: There was a statistically significant difference between the groups (chi-square test, P < 0.05) for the genotype of the VDR Fok I start codon polymorphism. The odds ratio (95% confidence interval) for the C allele in those at risk of stone disease was 1.672 (1.149-2.432). CONCLUSIONS: These results suggest that the VDR Fok I start codon polymorphism may be a good candidate for a genetic marker in calcium oxalate stone disease.

Adult↗
PubMed1999

Two different mutations in the same codon of a type II hair keratin (hHb6) in patients with monilethrix.

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. Mutations of the helix-encoding region in two hair-specific keratins (hHb1 and hHb6) have been identified. We have now investigated two unrelated monilethrix patients and identified two different novel heterozygous point mutations of the same codon in exon 7 of the hHb6 gene. Dystrophic hair samples obtained from both patients showed the typical beaded appearance by scanning electron microscopy. Both mutations affected the first base of codon 402 (glutamic acid). In patient A, a G to C transition occurred causing a glutamine substitution (GAG to CAG: E402Q) whereas in patient B, the transition was G to A yielding a lysine substitution (GAG to AAG: E402K). The sequence of the 1A helical regions of hHb1 and hHb6 as well as the 2B helical region of hHb1, were normal. Unaffected relatives did not have the hHb6 mutation and this codon was found to be highly conserved showing no alteration in the normal population (100 alleles examined). Both mutations disrupted a Taq I restriction site and restriction fragment length polymorphism analysis showed that a diagnostic 361 bp fragment could confirm the mutation. Thus, two new point mutations of the hair-specific keratin gene hHb6 have been identified in this genetic disease.

Alopecia↗
PubMed2001

Renal amyloidosis caused by a novel stop-codon mutation in the apolipoprotein A-II gene.

BACKGROUND: Although apolipoprotein A-II (apoA-II) associated amyloidosis has been described in the senescent accelerated mouse (SAM) model of aging, so far there has been no report of human apoA-II amyloidosis except for a recent report of renal amyloidosis resulting from a stop-codon to glycine mutation of apoA-II. The mechanisms of amyloid formation in human apoA-II amyloidosis are not clear. METHODS: A 46-year-old Caucasian male with proteinuria noted at 42 years of age was studied. Renal biopsy revealed amyloid deposition in glomeruli. DNA analysis of genes known to be associated with hereditary renal amyloidosis revealed no abnormalities. To elucidate the type of his amyloidosis, apoA-II gene and plasma apoA-II were examined. RESULTS: DNA analysis revealed heterozygosity for a G to C transversion at the second position of the stop-codon of apoA-II gene, suggesting a stop to serine substitution at codon 78. Western blot analysis and amino acid sequence analysis of the patient's plasma apoA-II showed both normal apoA-II and variant apoA-II with a 21-amino acid residue extension at the C-terminus. CONCLUSIONS: These results indicate that the patient's amyloid fibrils were derived from apoA-II and the amyloidogenesis is likely to be closely linked to the peptide extension at the C-terminus of variant apoA-II. The pathogenesis of human apoA-II amyloidosis is different from that of SAM.

Amino Acid Sequence↗
PubMed1996

Analysis of Ki-ras codon 12 mutations in the duodenal juice of patients with pancreatic cancer.

BACKGROUND & AIMS: Point mutations of the Ki-ras gene at codon 12 have been frequently identified in pure pancreatic juice of patients with pancreatic cancer in studies examining pancreatic cancer tissues. The aim of this study was to examine mutations of the Ki-ras codon 12 in the duodenal juice collected from patients with various pancreatic disorders. METHODS: The duodenal juice was collected through a Dreiling tube installed in the duodenum during a secretin test. Analysis of the Ki-ras mutations was performed using the enriched polymerase chain reaction--single-strand conformation polymorphism technique. RESULTS: Point mutations were detected in 12 of 19 patients with pancreatic cancer; of the 12 patients, 10 had ductal tubular adenocarcinoma and 2 intraductal papillary adenocarcinoma. Mutational patterns included GAT (n = 4), GTT (n = 3), CGT (n = 1), and double mutations of GTT and GAT (n = 3) and GAT and CGT (n = 1). In 41 patients with benign pancreatic disorders, a point mutation was detected in only 1 patient with chronic pancreatitis. CONCLUSIONS: Analysis of the Ki-ras codon 12 mutations in the duodenal juice is useful in the diagnosis of pancreatic cancer.

Base Sequence↗
PubMed2001

Immunoexpression of neurofibromin, S-100 protein, and leu-7 and mutation analysis of the NF1 gene at codon 1423 in osteofibrous dysplasia.

The NF1 (neurofibromatosis type 1, or von Recklinghausen disease) gene, is a tumor-suppressor gene, and its product, neurofibromin, down-regulates ras protein by its guanosine triphosphatase-activating protein (GAP)-related domain. Osteofibrous dysplasia (OFD) is characterized by fibroblast-like spindle cells and osseous tissue and is generally seen in the tibia or fibula during childhood. The precise nature of OFD remains controversial. Cosegregations of OFD and NF1 have been reported, and it has been surmised that OFD is associated with the NF1 gene. We studied the expressions of NF1 gene product (neurofibromin) and so-called Schwann cell markers (S-100 protein, Leu-7) in 17 cases of OFD immunohistochemically. Ten cases of fibrous dysplasia (FD) were also used for the purpose of comparison. Five OFD and 7 FD cases were analyzed for NF1 gene mutation at codon 1423, which is a GAP-related domain, by single-strand conformation polymorphism. Fibroblast-like cells of OFD showed the expression of neurofibromin (5 of 17), S-100 protein (9 of 17), and Leu-7 (5 of 17), and those of FD did not show these expressions, with the exception of 1 case that showed Leu-7 expression. Regarding the OFD cases, significant correspondence was found between cases showing expression of neurofibromin and S-100 protein, between cases showing expression of neurofibromin and Leu-7, and between cases showing expression of S-100 protein and Leu-7 (P < .01). NF1 gene mutation at codon 1423 was not detected in either the OFD (0 of 5) or FD (0 of 7) cases. These results seem to suggest the possible involvement of neurofibromin in the development of OFD, which is associated with the expression of Schwann cell markers (S-100 protein and Leu-7). Furthermore, NF1 gene mutation at codon 1423 did not seem to be related to OFD.

Adolescent↗
PubMed2004

Tissue-specific codon usage and the expression of human genes.

A diverse array of mechanisms regulate tissue-specific protein levels. Most research, however, has focused on the role of transcriptional regulation. Here we report systematic differences in synonymous codon usage between genes selectively expressed in six adult human tissues. Furthermore, we show that the codon usage of brain-specific genes has been selectively preserved throughout the evolution of human and mouse from their common ancestor. Our findings suggest that codon-mediated translational control may play an important role in the differentiation and regulation of tissue-specific gene products in humans.

Adult↗
PubMed2006

Codon-usage bias versus gene conversion in the evolution of yeast duplicate genes.

Many Saccharomyces cerevisiae duplicate genes that were derived from an ancient whole-genome duplication (WGD) unexpectedly show a small synonymous divergence (K(S)), a higher sequence similarity to each other than to orthologues in Saccharomyces bayanus, or slow evolution compared with the orthologue in Kluyveromyces waltii, a non-WGD species. This decelerated evolution was attributed to gene conversion between duplicates. Using approximately 300 WGD gene pairs in four species and their orthologues in non-WGD species, we show that codon-usage bias and protein-sequence conservation are two important causes for decelerated evolution of duplicate genes, whereas gene conversion is effective only in the presence of strong codon-usage bias or protein-sequence conservation. Furthermore, we find that change in mutation pattern or in tDNA copy number changed codon-usage bias and increased the K(S) distance between K. waltii and S. cerevisiae. Intriguingly, some proteins showed fast evolution before the radiation of WGD species but little or no sequence divergence between orthologues and paralogues thereafter, indicating that functional conservation after the radiation may also be responsible for decelerated evolution in duplicates.

Codon↗
PubMed2006

A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte maturation and causes thrombocytopenia.

We have generated mice from a N-ethyl-N-nitrosourea mutagenesis screen that carry a mutation in the translation initiation codon of Gata-1, termed Plt13, which is equivalent to mutations found in patients with acute megakaryoblastic leukemia and Down syndrome. The Gata-1 locus is present on the X chromosome in humans and in mice. Male mice hemizygous for the mutation (Gata-1Plt13/Y) failed to produce red blood cells and died during embryogenesis at a similar stage to Gata-1-null animals. Female mice that carry the Plt13 mutation are mosaic because of random inactivation of the X chromosome. Adult Gata-1Plt13/+ females were not anemic, but they were thrombocytopenic and accumulated abnormal megakaryocytes without a concomitant increase in megakaryocyte progenitor cells. Gata-1Plt13/+ mice contained large numbers of blast-like colony-forming cells, particularly in the fetal liver, but also in adult spleen and bone marrow, from which continuous mast cells lines were readily derived. Although the equivalent mutation to Gata-1Plt13 in humans results in production of GATA-1s, a short protein isoform initiated from a start codon downstream of the mutated initiation codon, Gata-1s was not detected in Gata-1Plt13/+ mice.

Alkylating Agents↗
PubMed1977

Codon specificity of UGA suppressor tRNATrp from Escherichia coli.

A synthetic polyribonucleotide, poly(U5,G), was used to study the codon specificity of wild-type and UGA suppressor tRNATrp from Escherichia coli. Phe (UUU) incorporation directed by this synthetic messenger is reduced somewhat by omission from the incubation mixtures of Val (GUU), Leu (UUG), or Cys (UGU). In contrast, omission of Cys stimulates Trp incorporation, and this effect is much more pronounced with the UGA suppressor tRNATrp than with wild-type tRNA. The apparent replacement of Cys by Trp is specific, because the omission of Val or Leu slightly inhibits Trp incorporation. These data suggest that the UGA suppressor tRNATrp can translate codons of the form UGN (N is any ribonucleotide). In other words, the suppressor tRNATrp translates codons that properly match two out of the three anticodon nucleotides.

Base Sequence↗
PubMed1978

"Two out of three": an alternative method for codon reading.

An alternative method for codon reading, whereby only the first two codon nucleotides are recognized by the anticodon, is discussed and the experimental evidence for this "two of three" reading method is reviewed. Misreading of codons by the "two out of three" method could pose a significant threat to the fidelity of protein synthesis unless the genetic code is organized in such a way as to prevent this method from being used when it might compromise translational fidelity. Inspection of the genetic code shows that it is arranged in such a way that the "two out of three" reading method can be used without translational errors.

Anticodon↗