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Results for “Codon, Terminator”

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At least 181 records · Page 10Linked to original sources

PubMed1991

Nonsense mutations affect C1 inhibitor messenger RNA levels in patients with type I hereditary angioneurotic edema.

Members of two unrelated families with type I hereditary angioneurotic edema (HANE) were found to have elevated levels of C1 inhibitor (C1INH) mRNA. DNA sequence analysis of PCR-amplified monocyte C1INH mRNA revealed normal and mutant transcripts, as expected in this disorder that occurs in heterozygous individuals. Single base mutations near the 3' end of the coding sequence were identified in affected members of each family. One mutation consisted of insertion of an adenosine at position 1304 which created a premature termination codon (TAA), whereas the second consisted of deletion of the thymidine at position 1298 which created a premature termination codon (TGA) 23 nucleotides downstream. These mutations are approximately 250 nucleotides upstream of the natural termination codon. Nuclear run-off experiments in one kindred revealed no difference in transcription rates of the C1INH gene between the patients and normals. C1INH mRNA half-life experiments were not technically feasible because of the prolonged half-life of the normal transcript. Dideoxynucleotide primer extension experiments allowed the differentiation of the normal and mutant transcripts. These studies showed that the mutant transcript was not decreased relative to the normal, and this therefore was at least partially responsible for the C1INH mRNA elevation. This elevation may be due to the decreased catabolism of the mutant transcript.

Angioedema↗

PubMed1983

Nucleotide sequence of the vaccinia virus thymidine kinase gene and the nature of spontaneous frameshift mutations.

Nucleotide sequencing of a 1,300-base-pair vaccinia virus DNA segment previously shown to contain a thymidine kinase (TK) gene revealed an uninterrupted reading frame of 177 codons capable of producing a polypeptide with a molecular weight of 20,102. Mapping of the TK mRNA by primer extension indicated a unique 5' end that precedes the initiation codon by only six nucleotides. Multiple 3' ends within a 10-nucleotide region, about 30 nucleotides beyond the termination codon, were located by nuclease digestion of DNA-RNA hybrids, and the length of the TK transcript, exclusive of polyadenylate, was estimated to be approximately 570 nucleotides. The region preceding the TK mRNA start site is extremely A + T rich and has sequence homologies with three other early genes. Genetic information is so compressed in this region of the DNA that the putative transcriptional regulatory sequence of the TK gene overlaps the coding sequence of a late gene. Only nine nucleotides separate the termination codon of the late gene from the initiation codon of the TK gene. Downstream, 66 nucleotides separate the TK termination codon from the apparent initiation codon of another early gene. The nature of three independent TK- mutants was revealed by nucleotide sequencing. Each has a nucleotide reiteration leading to a +1 frameshift and a nonsense codon downstream. The location of one frameshift mutation provided evidence that the first ATG is used for initiation of protein synthesis.

Amino Acid Sequence↗

PubMed1998

Cycloheximide facilitates the identification of aberrant transcripts resulting from a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa.

Patients with generalized atrophic benign epidermolysis bullosa often show decreased expression of type XVII collagen, a transmembrane hemidesmosomal protein encoded by COL17A1. This report documents a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa, and applies a new methodology to define and characterize the resulting mRNA splice variants. Mutational analysis of COL17A1 identified a maternally inherited G-to-T transversion at the -1 position of exon 32. This acceptor splice-site mutation led to the formation of aberrant transcripts present at extremely low levels. Based on our recent finding that cycloheximide stabilized mutant COL17A1 transcripts in keratinocytes homozygous for a frameshift mutation, the effects of the splice-site mutation on splicing of COL17A1 transcripts were determined using reverse transcriptase polymerase chain reaction of total RNA from keratinocytes incubated for 2.5 h in the presence or absence of 10 microg cycloheximide per ml. Using this approach, an abnormally spliced transcript was identified that contains an extra 264 bases upstream from exon 32, resulting in a premature termination codon 27 bp downstream from the cryptic splice site. Three other splice variants, including one derived from the skipping of exon 32, were also identified. These results indicate the usefulness of cycloheximide treatment in evaluating the abnormal processing of mRNA due to splice-site mutations, because: (i) aberrant splicing often generates a premature termination codon, (ii) transcripts with premature termination codons can occur at low or undetectable levels due to nonsense-mediated mRNA decay, and (iii) the levels of these transcripts can be increased by cycloheximide.

Adult↗

PubMed1999

Nonsense mutations in the alcohol dehydrogenase gene of Drosophila melanogaster correlate with an abnormal 3' end processing of the corresponding pre-mRNA.

From bacteria to mammals, mutations that generate premature termination codons have been shown to result in the reduction in the abundance of the corresponding mRNA. In mammalian cells, more often than not, the reduction happens while the RNA is still associated with the nucleus. Here, it is reported that mutations in the alcohol dehydrogenase gene (Adh) of Drosophila melanogaster that generate premature termination codons lead to reduced levels of cytoplasmic and nuclear mRNA. Unexpectedly, it has been found that the poly(A) tails of Adh mRNAs and pre-mRNAs that carry a premature termination codon are longer than in the wild-type transcript. The more 5' terminal the mutation is, the longer is the poly(A) tail of the transcript. These findings suggest that the integrity of the coding region may be required for accurate mRNA 3' end processing.

Alcohol Dehydrogenase↗

PubMed1987

Nucleotide sequence of the Escherichia coli gene for lipid A disaccharide synthase.

The lpxB gene of Escherichia coli, believed to be the structural gene for lipid A disaccharide synthase, is located in the min 4 region of the chromosome. It is adjacent to and clockwise of the lpxA gene, which is thought to encode UDP-N-acetylglucosamine acyltransferase. Preliminary evidence suggests that lpxA and lpxB are cotranscribed in the clockwise direction and thus constitute part of a previously unknown operon (D. N. Crowell, M. S. Anderson, and C. R. H. Raetz, J. Bacteriol. 168:152-159, 1986). We now report the complete nucleotide sequence of a 1,522-base-pair PvuII-HincII fragment known to carry the lpxB gene. This sequence contained an open reading frame of 1,149 base pairs, in agreement with the predicted size, location, and orientation of lpxB. There was a second open reading frame 5' to, and in the same orientation as, lpxB that corresponded to lpxA. The ochre codon terminating lpxA was shown to overlap the methionine codon identified as the initiation codon for lpxB, suggesting that these genes are cotranscribed and translationally coupled. A third open reading frame was also shown to begin at the 3' end of lpxB with analogous overlap between the opal codon terminating lpxB and the methionine codon that putatively initiates translation downstream of lpxB in the clockwise direction. These results argue that at least three genes constitute a translationally coupled operon in the min 4 region of the E. coli chromosome. The accompanying paper by Tomasiewicz and McHenry (J. Bacteriol. 169:5735-5744, 1987) presents 4.35 kilobases of DNA sequence, beginning at the 3' end of lpxB, and argues that dnaE and several other open reading frames may be members of this operon.

Acyltransferases↗

PubMed1994

The translational termination signal database (TransTerm) now also includes initiation contexts.

The TransTerm database of termination codon contexts has been extended to include sense codon usage, and initiation codon contexts. The database was constructed from 23,721 coding sequences from 93 organisms. The database contains: a) the sequence around the termination codon (-10, +10); b) the sequence around the initiation codon (-20, +10); c) the length, 'G+C%' of the third position of codons (GC3), the 'codon adaptation index' (CAI) and the 'effective number of codons' statistic (Nc); d) summary tables for each organism including total codon usage, stop codon and tetranucleotide stop-signal usage, and matrices tallying base frequencies at each position around the initiation and termination codons. The data are arranged to facilitate investigation of the relationships between the three phases of protein synthesis. The database is available electronically from EMBL.

Animals↗

PubMed1998

Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients.

Hypophosphatasia (HOPS) is an inherited disorder characterized by defects in skeletal mineralization due to the deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). To date, various mutations in the TNSALP gene have been identified. Especially, a deletion of T at position 1735 (1735T-del) located in exon 12 has been detected in three genetically unrelated Japanese patients, which seems to be one of the hot spots among the causative mutations in Japanese HOPS patients. 1735T-del causes a frame shift downstream from codon 503 (Leu), and consequently the normal termination codon at 508 is eliminated. Since a new inframe termination codon appears at codon 588 in the mutant DNA, the resultant protein is expected to have 80 additional amino acids. Expression of the mutant TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant 1735T-del had undetectable ALP activity, and its molecule size was larger than normal, as expected. Interestingly, an immunoprecipitation study of patients' sera using antibody against TNSALP revealed an abnormal protein which corresponded in size to the mutated TNSALP expressed by COS-1 cells, suggesting that the abnormal TNSALP is made by HOPS patients. The detection of TNSALP in cells transfected with 1735T-del using an immunofluorescent method exhibited only a faint signal on the cell surface, but an intense intracellular fluorescence after permeabilization.

Alkaline Phosphatase↗

PubMed1999

Conserved features at the 5 end of Drosophila R2 retrotransposable elements: implications for transcription and translation.

R2 non-LTR retrotransposable elements insert site-specifically into the 28S ribosomal genes of insects. The sequence of the 5' end of full-length R2 elements from thirteen species of Drosophila were compared. Sequences within the 5' untranslated region (5' UTR) revealed little to suggest the presence of a promoter. Protein translation initiates within the 5' UTR and requires the bypassing of a highly conserved termination codon preceding the single R2 open reading frame. This bypassing probably involves a conserved RNA secondary structure which brings a potential initiation codon into close proximity to this termination codon. The most highly conserved sequence within the 5' UTR has properties similar to internal ribosomal entry sites. Based on these findings, we propose that R2elements are co-transcribed with the 28S gene and are translated as part of a large ribosomal subunit.

5' Untranslated Regions↗

PubMed1995

Identification of several alpha-globin gene variations in a small Laotian family.

The present study concerns the identification of four alpha-globin gene deficiencies, one alpha 1-globin gene mutation, and one beta-globin gene mutation in a Laotian couple and their newborn baby. The parents were Hb E heterozygotes and the baby was an Hb E homozygote. The father carried the 4.2-kb deletion on one chromosome and a TAA-->CAA mutation at the terminating codon of the alpha 2-gene (Hb Constant Spring or CS) on the other chromosome. Moreover, the remaining alpha 1-globin gene on the chromosome with the 4.2-kb deletion was mutated at codon 74 (GAC-->CAC; Asp-->His; Hb Q-Thailand). The mother had the 3.7-kb deletion on one chromosome and a TAA-->TAT mutation at the terminating codon of the alpha 2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations and, at birth, had a high level of Hb Bart's (16.6%) reflecting a mild form of Hb H disease.

Adult↗

PubMed1987

Isolation of a rat mitochondrial release factor. Accommodation of the changed genetic code for termination.

A single release factor has been isolated and partially purified from rat mitochondria. It requires ethanol in addition to the specific termination codon when assayed in a heterologous system with Escherichia coli ribosomes. The factor recognizes the codons UAA and UAG but not UGA, and therefore it has been designated mtRF-1. A factor of the bacterial RF-2 type, which in E. coli recognizes UGA, or of the mammalian type, which recognizes all three termination codons, has not been detected in mitochondria. The absence of a factor responding to UGA accommodates the use of this codon as a signal for tryptophan in the rat mitochondrial genetic code. The mtRF-1 could translate all of the known termination codons in the rat mitochondrial genome. It does not respond to AGG and AGA which in bovine and human mitochondrial DNA code for termination but which in rat mitochondria may not code for either an amino acid or for termination.

Animals↗

PubMed1997

Reassessing the organization of the UL42-UL43 region of the human cytomegalovirus strain AD169 genome.

A polymorphism in the UL42-UL43 region of the human cytomegalovirus genome has been characterized by nucleotide sequence analysis, revealing a 929-bp insertion following nt 54,612 relative to the published strain AD169-UK genome sequence (M.S. Chee et al., 1990, Curr. Top. Microbiol Immunol. 154, 125-170). Although AD169-UK exhibited polymorphism in this genomic region, other CMV strains (Towne, Toledo, and AD169-ATCC) carried only the newly characterized longer form. The additional sequence altered the assignment of UL42 and UL43 open reading frames. UL42 decreased in size from 157 to 125 codons, retaining 76 of the previously reported carboxyl terminal codons, and UL43 increased in size from 187 to 423 codons, retaining 185 of the previously reported amino terminal codons. This additional sequence makes UL43 a more conserved betaherpesvirus US22 family member. Only AD169-UK exhibited restriction fragment length polymorphism in this region, suggesting that a deletion occurred during the propagation of this strain in cell culture. The additional sequence should be considered a bona fide part of the cytomegalovirus genome and the AD169 genome size should be corrected to 230,283 bp.

Amino Acid Sequence↗

PubMed1996

Clinicopathological correlations of compound heterozygous COL7A1 mutations in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa is an inherited mechano-bullous disorder of skin and mucous membranes. Ultrastructurally, the disease is characterized by abnormalities of anchoring fibrils, attachment structures below the epidermal basement membrane, composed of type VII collagen. Mutations in the type VII collagen gene (COL7A1) have been shown conclusively to underlie dystrophic epidermolysis bullosa. Since there is variation of the phenotype, accompanied by heterogeneous anchoring fibril morphology and type VII collagen immunostaining, it is conceivable that different types and combinations of COL7A1 mutations correlate with different phenotypes. We therefore screened recessive dystrophic epidermolysis bullosa patients for COL7A1 mutations. Three unrelated patients showed the same premature termination codon mutation in exon 13 of one allele, yet they were all compound heterozygotes, each having a different mutation in the second allele. The first patient had a premature termination codon within the collagenous region of COL7A1 associated with severe disease, absent anchoring fibrils and undetectable type VII collagen immunostaining. The second had a premature termination codon in the non-collagenous NC-2 region associated with severe disease, wispy anchoring fibrils, and patchy type VII collagen immunostaining. The third had a glycine-to-aspartic acid substitution within the collagenous region, associated with milder disease, no identifiable anchoring fibrils, but near normal type VII collagen immunostaining. We conclude that the nature and position of mutations within COL7A1 correlate with specific disease features and may provide an insight into the molecular mechanisms of anchoring fibril formation and epidermal-dermal adhesion.

Adult↗

PubMed1996

The nucleotide sequence of RNA-1 of Indian peanut clump furovius.

The nucleotide sequence of RNA-1 of an isolate of the H serotype of Indian peanut clump virus (IPCV-H) was shown to comprise 5,841 nucleotides. The RNA contains three open reading frames (ORF) which are between nucleotides 133 and 3,522, nucleotides 3,526 and 5,103 (assuming expression by suppression of the ORF 1 termination codon) and nucleotides 5,168 and 5,539. The encoded polypeptides have M(r), of 129,687 (p130), 60,188 (p60) and 14,281 (p14). ORF 2 is thought to be expressed by suppression of the termination codon of ORF 1 to produce a M(r) 189,975 product (p190). p130 contains sequences characteristic of proteins with methyl transferase and NTP-binding properties and p190 contains these and sequences characteristic of RNA-dependent RNA polymerases. The nucleotide sequence of IPCV RNA-1 is similar to that of peanut clump virus (PCV) and corresponding encoded polypeptides are 88% (p130), 95% p60 and 75% (p14) identical. The sequences of the translation products are also similar to those of soil-borne wheat mosaic virus and barley stripe mosaic virus. Oligonucleotide primers, designed on the basis of the sequences of RNA-1 of IPCV and PCV, were effective in reverse transcription-PCR amplification of these RNAs and that of IPCV isolates of the serologically distinct L and T serotypes.

Amino Acid Sequence↗

PubMed1996

The alpha / beta and alpha 2 / alpha 1-globin mRNA ratios in different forms of alpha-thalassemia.

The present study provides information about the alpha / beta and alpha 2 / alpha 1-mRNA ratios in reticulocytes of normal adults and individuals with different alpha-globin gene deficiencies; it found its origin in analytical data of blood samples from a Laotian couple and their newborn baby. The father carried the 4.2 kb deletion on one chromosome and a TAA --> CAA mutation at the terminating codon of the alpha 2 gene (Hb Constant Spring or CS) on the other chromosome. The mother had the 3.7 kb deletion on one chromosome and a TA A --> TAT mutation at the terminating codon of the alpha 2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations. The mRNA data for this family were compared to those for persons with several well-defined alpha-globin gene deficiencies. The results confirm the importance of the alpha 2 alpha 1-mRNA for the synthesis of alpha chains in alpha-thalassemia-2 homozygotes (-alpha/-alpha) and in patients with Hb H disease due to the deletion of three alpha-globin genes (-alpha/--). Furthermore, the MRNA production of the alpha 1-globin gene on the chromosome with the alpha CS mutation (alpha CS alpha) is only one-half of that by the alpha 2 alpha 1-globin gene of a chromosome with a 3.7 or 4.2 kb deletion, explaining the greater severity of, and higher Hb H level in Hb H patients with the alpha CS alpha condition (alpha CS alpha/--) as compared to those with the three gene deletion (-alpha/--). The methodology could be useful as a preliminary screening for the presence of point mutations leading to the functional loss of a single alpha-globin gene, provided common deletional alleles have been excluded.

Adult↗

PubMed1999

Severe autosomal dominant retinitis pigmentosa caused by a novel rhodopsin mutation (Ter349Glu). Mutations in brief no. 208. Online.

Mutations in the rhodopsin gene are reported to be responsible for approximately 25% of all cases of autosomal dominant Retinitis pigmentosa (adRP). Affected individuals from a large family with an unusually severe form of adRP were screened for mutations in the rhodopsin gene. Direct sequencing of exon 5 revealed a TAA to GAA transversion at nucleotide 5276/codon 349, which was confirmed by Dde1 restriction digest analysis. This change would replace the normal termination codon with a glutamic acid residue (Ter-349-Glu, or X349E). The next predicted termination codon (TAA) lies 153bp downstream at nucleotides 5429 to 5431. Termination of transcription at this point would add an additional 51 amino-acid residues to the carboxy terminus of the rhodopsin molecule. This mutation is unique in producing a mutant rhodopsin in which all of the normal 348 amino-acid residues remain intact. It produces one of the most severe adRP phenotypes ever observed in a family with a rhodopsin mutation. In view of this the Ter-349-Glu mutation is worthy of further investigation to determine how the presence of this particular mutant opsin leads to rod photoreceptor degeneration.

Amino Acid Substitution↗

PubMed1996

Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease.

The Gag-Pol polyprotein of human immunodeficiency virus type 1 is not required for efficient viral particle assembly or release. However, in this report we demonstrate that the synthesis of a truncated Gag-Pol precursor due to a premature termination codon in pol can reduce the ability of a full-length provirus to direct the formation of viral particles. Marked effects on particle production were seen when premature termination codons were introduced into the integrase (IN)-coding region. By contrast, a mutant which lacked both IN and reverse transcriptase (RT) formed particles with normal efficiency. Particle production by IN mutants was restored to wild-type levels when a second premature termination codon was introduced at the 5' end of the RT-coding sequence. Particle formation was similarly restored by a second site mutation in the viral protease (PR) gene which prevented proteolytic processing of the Gag polyprotein. Finally particle formation was restored in the presence of A77003, a specific inhibitor of human immunodeficiency virus type 1 PR. These results suggest that the effects of a lack of IN sequences on particle formation require the synthesis of a Gag-Pol precursor which contains RT sequences and are due to inappropriate PR activity.

Animals↗

PubMed1994

Structure of the mouse arylsulfatase A gene and cDNA.

The murine arylsulfatase A (ARSA) gene and cDNA have been cloned and sequenced. The gene is 3.8 kb long and contains eight exons. All intron/exon splice junctions conform to the GT/AG consensus sequence. The genomic structure is similar to that of the human gene. One major RNA species of 3.2 kb is transcribed. This RNA species has a 5' untranslated region of 638 nucleotides and terminates in a region around nucleotide 700 downstream of the termination codon. In addition, a rare mRNA species terminating at a polyadenylation signal 135 nucleotides downstream of the termination codon has been found. A larger transcript of 4 kb can be detected in liver. The size difference is due to initiation of transcription 5' of the cap site of the 3.2-kb mRNA species. The entire ARSA cDNA has been cloned by PCR from reverse-transcribed RNA. The coding sequence has 1518 nucleotides and predicts a protein of 506 amino acids. The nucleotide as well as the amino acid sequence is highly conserved among humans and mice.

Amino Acid Sequence↗

PubMed1987

Nucleotide sequence analysis of RepFIC, a basic replicon present in IncFI plasmids P307 and F, and its relation to the RepA replicon of IncFII plasmids.

RepFIC is a basic replicon of IncFI plasmid P307 which is located within a 3.09-kilobase SmaI fragment. The nucleotide sequence of this region has been determined and shown to be homologous with the RepFIIA replicon of IncFII plasmids. The two replicons share three homologous regions, HRI, HRII, and HRIII, which are flanked by two nonhomologous regions, NHRI and NHRII. A comparison of coding regions reveals that the two replicons have several features in common. RepFIC, like RepFIIA, codes for a repA2 protein with its amino-terminal codons in HRI and its carboxy-terminal codons in NHRI. Although the codons for the repA1 proteins are located in NHRII, the DNA region containing a putative promoter, ribosomal binding site, and initiation codons is located in HRII. This region also codes for an inc RNA. There are nine base-pair differences between the inc RNA of RepFIIA and that of RepFIC, and as a result, RepFIC and RepFIIA replicons are compatible. An EcoRI fragment from the F plasmid which shows homology with RepFIC of P307 has also been sequenced. This fragment contains only a portion of RepFIC, including the genes for the putative repA2 protein and inc RNA. The region coding for a putative repA1 protein is interrupted by the transposon Tn1000 and shows no homology with the repA1 region of RepFIIA and RepFIC of P307. Our comparative and structural analyses suggest that RepFIC and RepFIIA, although different, have a similar replication mechanism and thus can be assigned to the same replicon family, which we designate the RepFIIA family.

Base Sequence↗