Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genes, Overlapping”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed2001

Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7.

Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer. Potent tumor suppressor genes located in this region encode transforming growth factor beta (TGF-beta) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF-beta-mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large-scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD7 appears to be more frequently amplified (10%) than the three other genes (4-7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF-beta signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene.

Chromosome Deletion↗
PubMed1999

YMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: A study by in vitro full-length viral DNA transfection.

Recently, lamivudine used to treat patients with hepatitis B virus (HBV) infection was revealed to have potent antiviral activity. However, HBV resistance to lamivudine has been reported and shown to have amino acid substitutions in the methionine residue of the conserved tyrosine (Y), methionine (M), aspartate (D), aspartate (D) motif of RNA-dependent DNA polymerase. To explore the consequences of substitutions in this motif (YMDD), we made 7 variants by substituting the methionine of the YMDD motif with isoleucine (I), valine (V), alanine (A), leucine (L), lysine (K), arginine (R), and threonine (T). Replication ability of these variants was evaluated by transfection into human hepatoma cells. Sensitivity to lamivudine was tested for replication-competent variants. Four variants with hydrophobic substitutions (I, V, A, and L) remained replication-competent, whereas 3 others with hydrophilic substitutions (K, R, and T) exhibited impaired replication. Of the 4 replication-competent variants, 2 (I and V) were resistant, and 2 (A and L) were sensitive to lamivudine. Because the polymerase and the surface gene overlap, the introduction of these mutations affected the secretion of hepatitis B surface antigen (HBsAg), namely 4 variants (I, V, L, and R) secreted HBsAg, whereas 3 variants (A, K, and T) did not. Our study elucidated that only one amino acid substitution in the YMDD motif was sufficient to cause lamivudine resistance in vitro. As a result of replication competence and lamivudine sensitivity, only viruses having YIDD or YVDD sequences may appear during treatment with lamivudine. This in vitro system could be used to study HBV mutations, replication competence, and their susceptibility to antivirals.

Amino Acid Sequence↗
PubMed1987

Amino acid sequence of the cytochrome subunit of the photosynthetic reaction centre from the purple bacterium Rhodopseudomonas viridis.

The complete nucleotide sequence of the gene encoding the cytochrome subunit of the photosynthetic reaction centre from the purple bacterium Rhodopseudomonas viridis, and the derived amino acid sequence are presented. The nucleotide sequence of the gene reveals the existence of a typical bacterial signal peptide of 20 amino acid residues which is not found in the mature cytochrome subunit. The gene encoding the cytochrome subunit is preceded by the gene encoding the M subunit. Both genes overlap by 1 bp. The mature cytochrome subunit consists of 336 amino acid residues; 73% of its amino acid sequence was confirmed by protein sequencing work. The mol. wt of the cytochrome subunit including the covalently bound fatty acids and the bound heme groups is 40 500. The internal sequence homology is low, despite the symmetric structure of the cytochrome subunit previously shown by X-ray crystallographic analysis of the intact photosynthetic reaction centre. Sequence homologies to other cytochromes were not found.

Journal Article↗
PubMed2004

Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns.

High-throughput analysis of RNA molecules in multicellular eukaryotes has revealed an abundance of complementary antisense RNAs that are transcribed from separate or overlapping genes. In mammals these include many novel non-coding RNAs of unknown function. This unexpected complexity of the mammalian transcriptome suggests that expression of many genes is regulated post-transcriptionally by mechanisms mediated by RNA-RNA base pairing. The recent discovery of the widespread expression of microRNAs in animals and plants provides a prototypic example of such regulation in eukaryotes. However, there are likely to be numerous other types of antisense regulation in eukaryotes, many as yet uncharacterized.

Animals↗
PubMed1994

Genetic evidence for IS1 transposition regulated by InsA and the delta InsA-B'-InsB species, which is generated by translation from two alternative internal initiation sites and frameshifting.

Insertion sequence IS1 contains two reading frames, insA and B'-insB, which are responsible for its transposition, and was previously shown to express two proteins. The first, InsA, is the product of insA. The second, InsA-B'-InsB is a fusion of InsA with the product of B'-insB. Synthesis of this protein occurs by a -1 frameshift from the 3' region of the insA frame to the open reading frame B', extending from the 5' end of the insB frame. Here, I have shown genetically that IS1 encodes the third species delta InsA-B'-InsB: delta InsA-B'-InsB uses two alternative initiation codons in the middle of the insA frame, and is produced by a frameshift mechanism similar to that used in InsA-B'-InsB expression. Deletion of the small region preceding these initiation codons resulted in decreased expression of delta InsA-B'-InsB, suggesting that the small region play some role in the translation initiation. Surprisingly, it was found that delta InsA-B'-InsB has a transposase-like function and InsA can stimulate the transposition promoted by delta InsA-B'-InsB, while delta InsA-B'-InsB seemed to bind to the left terminal inverted repeat (IRL) of IS1 and inhibit transposition when it was present in excess, as well as InsA represses transposition. It is likely that IS1 transposition activity depends on the ratio of InsA to delta InsA-B'-InsB. A double missense mutation of the internal initiation codons resulted in decreased cointegration activity, showing that delta InsA-B'-InsB is responsible for transposition but InsA-B'-InsB is probably not. Some IS elements, which also contain two tandem, out-of-phase, overlapping genes, appear to express deleted fusion proteins like delta InsA-B'-InsB, but the functions are unknown. The complex phenomena of transposition and its control found in IS1 may be more general in the other mobile DNAs.

Amino Acid Sequence↗
PubMed2000

A core-promoter region functions bi-directionally for human opioid-receptor-like gene ORL1 and its 5'-adjacent gene GAIP.

We report the genomic structure and functional activities of the promoter regions of the human opioid-receptor-like gene ORL1 and its 5'-adjacent gene GAIP (G alpha interacting protein). The transcription and alternative splicing of human ORL1 are controlled by two alternate promoters, located approximately 10 kb apart. The two promoter regions lack a TATA-box and are GC rich. Promoter 1A initiates, from a single transcription start point (TSP), two transcripts: one consisting of exons 1A, 1B, 2, etc., the other without exon 1B. A potential ATG codon upstream of the initiation codon of ORL1 starts a new open-reading frame encoding a theoretical polypeptide of 205 amino acid residues. The promoter 1B transcribes, from multiple TSPs, only one mRNA starting with exon 1B. Two different repeat sequence polymorphisms are found in the ORL1 promoter regions. Luciferase reporter gene assays with promoter regions and a series of deletion mutants have mapped the core-promoter 1A and 1B within two short fragments. DNA sequencing and a database search reveal that the human GAIP gene is located upstream of ORL1 and is oriented in the opposite direction. The transcription and alternative splicing of GAIP are also under the control of alternate promoters. The first exons of ORL1 and GAIP are separated by only 83 bp. This 83 bp fragment, together with short surrounding sequences from both first exons, functions bi-directionally as a core-promoter for both genes. The transcription and alternative splicing of human ORL1 and GAIP are cell-type specific. While GAIP is expressed in both NT2 precursor cells and differentiated NT2 neuronal cells, ORL1 is only expressed in differentiated NT2 neurons. Since ORL1 is a G protein-coupled receptor and GAIP interacts with G protein alpha subunits, their physical linkage in the genome and co-operative transcriptional regulation may play a significant role in ORL1 receptor signal transduction.

Alternative Splicing↗
PubMed1991

Pleiotropic action of the murine quaking locus: structure of the qkv allele.

The spontaneous allele quakingviable (qkv) exerts effects on myelination and spermiogenesis. The defects generated by qkv were not separated in a multilocus mapping cross that provided a mapping resolution of 0.1 centiMorgans (cM). Furthermore, no distortions suggestive of a large chromosomal anomaly associated with qkv were apparent. One plausible interpretation is that the quaking locus contains more than one functional domain, either organized into overlapping genes or expressed by alternative splicing mechanisms. The cloning needed to analyze this locus will be enhanced by the very high resolution of the meiotic mapping cross reported here. The recombinational distances on this qkv map were compressed compared with those previously reported in a high-resolution map for qkl-1, an embryonic lethal allele of quaking induced by ethylnitrosourea. Additional crosses confirmed prior reports that the sex and the genetic background of the heterozygous parent can affect recombinational distances. These joint effects on recombination are strong enough to account for the discrepancy between the two maps. This variability of two-factor map values leads to the preferred multilocus map-building protocol discussed in the accompanying paper.

Animals↗
PubMed1987

Overlapping transcription units in the transient receptor potential locus of Drosophila melanogaster.

We report the identification in Drosophila melanogaster of two mRNA transcripts that are derived from the transient receptor potential locus by transcription in opposite directions. The two transcripts overlap; one transcript has, as part of its 5'-untranslated sequence, the reverse complement of 442 bp of the 3' terminus of the transcript derived from the opposite DNA strand. Conceptual translation of the corresponding cDNA sequences predicted for one of the transcripts a polypeptide whose C terminus shares sequence and structural similarity with the cell-wall-binding domain of protein A from Staphylococcus aureus; for the transcript derived from the opposite DNA strand, a polypeptide of 264 amino acids was predicted, which showed no significant sequence homology with any known protein. The two transcripts have different tissue specificities: one is expressed predominantly in the eye and the other is in the body. These findings may have implications in the relationship between the organization of overlapping genes on opposite DNA strands and regulation of gene expression by antisense RNA.

Amino Acid Sequence↗
PubMed2006

Cloning and characterization of a beta-galactosidase encoding region in Lactobacillus coryniformis CECT 5711.

A chromosomal DNA fragment of 7.8 kb from Lactobacillus coryniformis CECT 5711 was cloned in Escherichia coli K-12 and was found to express a functional beta-galactosidase. Nucleotide sequence analysis showed that this fragment contained two partially overlapping genes, the lacL (1,881 bp) and the lacM (960 bp), that encode the subunits of a heterodimeric beta-galactosidase, with estimated molecular masses of 72,129 and 35,233 Da, respectively. Other three incomplete open reading frames showing homology to another beta-galactosidase, an alpha-galactosidase, and a galactokinase, respectively, were also found. The L. coryniformis beta-galactosidase was overproduced in E. coli by using an isopropyl-beta-D: -thiogalactopyranoside (IPTG) expression system. Two new proteins with an estimated M (r) s of approximately 72,000 and 35,000 appeared upon induction with IPTG, and extracts of the recombinant E. coli strain showed beta-galactosidase activity.

Base Sequence↗
PubMed2003

The complete nucleotide sequence of Subterranean clover mottle virus.

The complete nucleotide sequence of Subterranean clover mottle virus (SCMoV) genomic RNA has been determined. The SCMoV genome is 4,258 nucleotides in length. It shares most nucleotide and amino acid sequence identity with the genome of Lucerne transient streak virus (LTSV). SCMoV RNA encodes four overlapping open reading frames and has a genome organisation similar to that of Cocksfoot mottle virus (CfMV). ORF1 and ORF4 are predicted to encode single proteins. ORF2 is predicted to encode two proteins that are derived from a -1 translational frameshift between two overlapping reading frames (ORF2a and ORF2b). A search of amino acid databases did not find a significant match for ORF1 and the function of this protein remains unclear. ORF2a contains a motif typical of chymotrypsin-like serine proteases and ORF2b has motifs characteristically present in positive-stranded RNA-dependent RNA polymerases. ORF4 is likely to be expressed from a subgenomic RNA and encodes the viral coat protein. The ORF2a/ORF2b overlapping gene expression strategy used by SCMoV and CfMV is similar to that of the poleroviruses and differ from that of other published sobemoviruses. These results suggest that the sobemoviruses could now be divided into two distinct subgroups based on those that express the RNA-dependent RNA polymerase from a single, in-frame polyprotein, and those that express it via a -1 translational frameshifting mechanism.

Amino Acid Sequence↗
PubMed1998

Characterization of Trichomonas vaginalis virus proteins in the pathogenic protozoan T. vaginalis.

The 4.6-kb double-stranded (ds) RNA of Trichomonas vaginalis virus (TVV)-T1 has been shown to encode two overlapping genes, cap and pol. In this study, a serum for specifically detecting viral cap gene product was raised against a recombinant protein, and sera for specifically detecting pol gene product were raised against synthetic oligopeptides. A 75-kDa major protein and a 160-kDa minor protein were detected by anti-CAP serum in a TVV-T1 sample, indicating that the 75-kDa protein is the viral capsid protein. The 160-kDa protein alone was also detected by two distinct anti-POL sera, indicating that the pol gene is expressed as a CAP-POL fusion protein. These results suggest that the TVV-T1 genome is arranged into a cap-pol organization in a manner similar to that of viruses in family Totiviridae.

Animals↗
PubMed1988

Analysis of the in vitro translation products of the equine herpesvirus type 1 immediate early mRNA.

Equine herpesvirus type 1 (EHV-1) gene expression is coordinately regulated in an alpha, beta, gamma fashion. Viral alpha gene products include a 6.0-kb immediate early (IE) mRNA species (W. L. Gray et al., 1987, Virology 158, 79-87) and at least four closely related IE polypeptides (IEPs) (G.B. Caughman et al., 1985, Virology 145, 49-61). In this report, we describe results obtained from a series of in vitro translation experiments which were performed in an effort to characterize the IEPs and identify the mechanism by which individual IE protein species are generated. Our data indicate that a family of IEPs is generated in vitro from the 6.0-kb mRNA size class and that these IEPs correspond in overall size and antigenicity to those synthesized in infected cells. Using time-course/pulse-chase analyses, we show that production of three of the major IEPs [IE1' (193 kDa), IE3' (166 kDa), and IE4' (130 kDA)] occurs concomitantly, that none of these protein species can be chased completely into another, and that at least two additional minor species appear to be processed following synthesis. Finally, we show that the 6.0-kb mRNA species isolated during early or late stages of the infection cycle can be translated to yield all of the major IE proteins, indicating that production of the family of IEPs is not dependent upon accumulation of the IE mRNA which occurs during a cycloheximide blocked infection cycle. The implications of these findings are discussed as they relate to the origin and production of the IEPs both in vivo and in vitro.

Blotting, Northern↗
PubMed1989

Transposon mutagenesis of baculoviruses: analysis of Trichoplusia ni transposon IFP2 insertions within the FP-locus of nuclear polyhedrosis viruses.

The transposable IFP2 element of Trichoplusia ni was originally isolated as a host DNA insertion in spontaneous FP mutants of Galleria mellonella or Autographa californica nuclear polyhedrosis viruses (NPVs). The termini of IFP2 insertions from five independently isolated FP mutants were sequenced. In all cases IFP2 is flanked by 13-bp terminal inverted repeats and has additional inverted repeats of 19 bp in length located asymmetrically with respect to the ends of the element. Insertion of IFP2 into the viral genome always generated a duplication of the tetranucleotide target site, TTAA. There was an apparent preference for insertion within a 12-bp A + T-rich imperfect palindromic sequence surrounding the target site. Sequence analysis of three independent IFP2 elements revealed an internal domain of 2.475 kb containing an RNA polymerase II promoter region and two large open reading frames. Primer extension analysis of IFP2-specific mRNA positioned the 5' terminus of the transcript. The element is present in DNA isolated from T. ni cell lines TN-368 and TN-5B1, but is not apparent in DNAs isolated from the TN-R2 cell line or our laboratory colony of T. ni larvae, suggesting IFP2 was recently introduced into the T. ni genome.

Base Sequence↗
PubMed1996

Olfaction in Drosophila: from odor to behavior.

Odors elicit a variety of behavioral responses from Drosophila via a relatively simple, but sensitive, olfactory system. An increasing number of mutants have been found to be defective in olfactory function. Genetic and molecular analyses of the Drosophila olfactory system have identified some of its molecular components, and have revealed some principles of its function and organization.

Animals↗
PubMed1988

Molecular cloning and characterization of cellular genes whose expression is repressed by the adenovirus E1a gene products and growth factors in quiescent rat cells.

Several cDNA clones of cellular genes, whose expression is repressed by the adenovirus type-12 E1a gene products, were isolated from a rat 3Y1 cell cDNA library by differential plaque hybridization with labeled cDNA probes prepared from 3Y1 and the derivative cell line expressing the E1a gene constitutively. The changes in the levels of these gene transcripts during cell-cycle progression from G0 to G1 to S phase were analyzed with 3Y1 cells and gMA cell lines, derived from 3Y1 cells, in which the expression of the E1a gene or its 13S, 12S cDNA can be switched on by the addition of dexamethasone. Quantitation of the transcripts by Northern-blot hybridizations and by nuclear run-on experiments revealed the following. (i) The level of clone-53 mRNA (which turned out to be the fibronectin (FN)-coding mRNA) is very high in resting gMA cells and decreased rapidly after switching on of the E1a gene or its 13S, or 12S cDNA. (ii) The addition of serum or platelet-derived growth factor to resting 3Y1 cells also resulted in a rapid decrease in the FN mRNA level, but the addition of epidermal growth factor (EGF) had little or no effect. (iii) The level of clone-56 mRNA in gMA cells was not affected by the induction of the E1a gene expression; however, the addition of EGF to resting gMA or 3Y1 cells resulted in a decrease of this mRNA after a 12- to 16-h lag period. Induction of the E1a gene expression in gMA cells treated with EGF shortened the lag period. The addition of serum to resting 3Y1 cells decreased the clone-56 mRNA level without a significant lag period.

Adenoviridae↗
PubMed1995

Completion of a cDNA sequence from a tobamovirus pathogenic to crucifers.

Turnip vein-clearing virus (TVCV) is a tobamovirus related to ribgrass mosaic virus. We report the nucleotide (nt) sequences of the 5'-untranslated region (UTR) and the 3'-half of the TVCV genome (the 3' region of the 182-kDa protein-encoding gene, as well as the movement protein and coat protein genes and the 3'-UTR). The determination completes the nt sequence of the cDNA of TVCV.

Amino Acid Sequence↗
PubMed2005

Endogenous siRNAs derived from a pair of natural cis-antisense transcripts regulate salt tolerance in Arabidopsis.

In higher eukaryotes, miRNAs and siRNAs guide translational inhibition, mRNA cleavage, or chromatin regulation. We found that the antisense overlapping gene pair of Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH), a stress-related gene, and SRO5, a gene of unknown function, generates two types of siRNAs. When both transcripts are present, a 24-nt siRNA is formed by a biogenesis pathway dependent on DCL2, RDR6, SGS3, and NRPD1A. Initial cleavage of the P5CDH transcript guided by the 24-nt siRNA establishes a phase for the subsequent generation of 21-nt siRNAs by DCL1 and further cleavage of P5CDH transcripts. The expression of SRO5 is induced by salt, and this induction is required to initiate siRNA formation. Our data suggest that the P5CDH and SRO5 proteins are also functionally related, and that the P5CDH-SRO5 gene pair defines a mode of siRNA function and biogenesis that may be applied to other natural cis-antisense gene pairs in eukaryotic genomes.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed2004

Hepatitis B virus: pathogenesis, viral intermediates, and viral replication.

Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1).

DNA, Viral↗