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At least 1,711 records · Page 95Linked to original sources
PubMed1984

Isolation and characterization of cloned DNA sequences containing ribosomal protein genes of Drosophila melanogaster.

Ribosomal (r) proteins encoded by polyadenylated RNA were specifically precipitated in vitro from polysomes by using antibodies raised against characterized Drosophila melanogaster r proteins. The immuno-purified mRNA in the polysome complex was used to prepare cDNA with which to probe a D. melanogaster genomic library. Selected recombinant phages were used to hybrid select mRNAs, which were analyzed by in vitro translation. Three clones containing the genes for r proteins 7/8, S18, and L12 were positively identified by electrophoresis of the translation products in one-dimensional and two-dimensional polyacrylamide gels. Sequences encoding r proteins S18 and L12 were found to be present in the genome in single copies. In contrast, the polynucleotide containing the region encoding 7/8 may be repeated or may contain or be flanked by short repeated sequences. The sizes of mRNAs that hybridized to the recombinant clone containing 7/8 were significantly larger than would be expected from the molecular weight of protein 7/8, implying that there were unusually long 5' and 3' noncoding sequences. The mRNAs for r proteins S18 and L12 were however, only about 10% larger. In situ hybridizations to salivary gland polytene chromosomes, using the recombinant phage, revealed that the recombinant clone containing the gene for r protein 7/8 hybridized to 5D on the X chromosome; the recombinant clone containing the gene for S18 hybridized to 15B on the same chromosome, and the recombinant phage containing the gene for L12 hybridized to 62E on chromosome 3L. It is of interest that the genomic locations of all three r protein clones were within the chromosomal intervals known to contain the Minute mutations [M(1)0, M(1)30, and M(3)LS2]. Although each clone contained sequences specifying two to four proteins, none had more than one identifiable r protein gene, suggesting that different D. melanogaster r protein genes may not be closely linked.

Animals↗
PubMed2025

Long non-coding RNA NEAT1 promotes colorectal cancer progression via interacting with SIRT1.

Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA, is found to be significantly dysregulated in different types of cancer, including colorectal cancer (CRC). Nevertheless, there is still much to learn about the precise functions and processes of NEAT1 in the progression of CRC. Using The Cancer Genome Atlas (TCGA) database and 50 CRC specimens from the First Affiliated Hospital of Dali University, we assessed the expression of NEAT1 to determine its clinical impact. Through gene set enrichment analysis (GSEA), Cancer Single-cell State Atlas (CancerSEA), and immune infiltration studies, we elucidated key functions of NEAT1. We utilized Cell Counting Kit-8 (CCK8), wound healing, and Transwell assays to investigate the role of NEAT1 in the progression of CRC. Through the use of GSEA and immunohistochemistry, additional investigations were conducted to unveil the downstream targets of NEAT1 and gain insights into their regulatory dynamics. Our in vitro studies confirmed the regulatory role of NEAT1 in CRC. Findings indicate that increased NEAT1 expression correlates with adverse outcomes in colorectal tissues. In the CRC model, reduced levels of NEAT1 lead to reduced cell proliferation, invasion, and migration. Additionally, NEAT1 influenced immune cell infiltration in CRC and functioned as an oncogene by upregulating Sirtuin 1 (SIRT1) expression. This study demonstrates that NEAT1 promotes CRC progression and metastasis through a SIRT1-mediated mechanism, suggesting its potential as a prognostic biomarker and therapeutic target for CRC.

RNA, Long Noncoding↗
PubMed2025

Structural basis of differential gene expression at eQTLs loci from high-resolution ensemble models of 3D single-cell chromatin conformations.

MOTIVATION: Techniques such as high-throughput chromosome conformation capture (Hi-C) have provided a wealth of information on nucleus organization and genome important for understanding gene expression regulation. Genome-Wide Association Studies have identified numerous loci associated with complex traits. Expression quantitative trait loci (eQTL) studies have further linked the genetic variants to alteration in expression levels of associated target genes across individuals. However, the functional roles of many eQTLs in noncoding regions remain unclear. Current joint analyses of Hi-C and eQTLs data lack advanced computational tools, limiting what can be learned from these data. RESULTS: We developed a computational method for simultaneous analysis of Hi-C and eQTL data, capable of identifying a small set of nonrandom interactions from all Hi-C interactions. Using these nonrandom interactions, we reconstructed large ensembles (×105) of high-resolution single-cell 3D chromatin conformations with thorough sampling, accurately replicating Hi-C measurements. Our results revealed many-body interactions in chromatin conformation at the single-cell level within eQTL loci, providing a detailed view of how 3D chromatin structures form the physical foundation for gene regulation, including how genetic variants of eQTLs affect the expression of associated eGenes. Furthermore, our method can deconvolve chromatin heterogeneity and investigate the spatial associations of eQTLs and eGenes at subpopulation level, revealing their regulatory impacts on gene expression. Together, ensemble modeling of thoroughly sampled single-cell chromatin conformations combined with eQTL data, helps decipher how 3D chromatin structures provide the physical basis for gene regulation, expression control, and aid in understanding the overall structure-function relationships of genome organization. AVAILABILITY AND IMPLEMENTATION: It is available at https://github.com/uic-liang-lab/3DChromFolding-eQTL-Loci.

Quantitative Trait Loci↗
PubMed1999

The genome nucleotide sequence of a contemporary wild strain of measles virus and its comparison with the classical Edmonston strain genome.

The only complete genome nucleotide sequences of measles virus (MeV) reported to date have been for the Edmonston (Ed) strain and derivatives, which were isolated decades ago, passaged extensively under laboratory conditions, and appeared to be nonpathogenic. Partial sequencing of many other strains has identified >/=15 genotypes. Most recent isolates, including those typically pathogenic, belong to genotypes distinct from the Edmonston type. Therefore, the sequence of Ed and related strains may not be representative of those of pathological measles circulating at that or any time in human populations. Taking into account these issues as well as the fact that so many studies have been based upon Ed-related strains, we have sequenced the entire genome of a recently isolated pathogenic strain, 9301B. Between this recent isolate and the classical Ed strain, there were 465 nucleotide differences (2.93%) and 114 amino acid differences (2.19%). Computation of nonsynonymous and synonymous substitutions in open reading frames as well as direct comparisons of noncoding regions of each gene and extracistronic regulatory regions clearly revealed the regions where changes have been permissible and nonpermissible. Notably, considerable nonsynonymous substitutions appeared to be permissible for the P frame to maintain a high degree of sequence conservation for the overlapping C frame. However, the cause and the effect were largely unclear for any substitution, indicating that there is a considerable gap between the two strains that cannot be filled. The sequence reported here would be useful as a reference of contemporary wild-type MeV.

3' Untranslated Regions↗
PubMed1998

Genomic sequence of physalis mottle virus and its evolutionary relationship with other tymoviruses.

The genome of physalis mottle tymovirus (PhMV) is 6673 nucleotides long and is rich in cytosine residues (40.58%) like other tymoviruses. The organization of the genes is also similar to that of five other tymoviruses whose sequences are known. However, PhMV has the longest 3' noncoding region as well as the longest replicase (RP) ORF. The RP sequences are similar to those of other tymoviruses (48-60% identity) whereas the coat proteins (CP) and the overlapping proteins (OP) are conserved to a lesser extent (30-50% and 26-34% respectively). A tetra peptide "GILG" was found to be present in all the tymoviral OPs. The PhMV RP also possesses the methyl transferase, polymerase and the helicase motifs found in all the Sindbis-like super group of plant viruses. A phylogenetic analysis of the six tymoviral sequences revealed that they do not have a rigid hierarchical similarity relationship.

Amino Acid Sequence↗
PubMed2003

Survey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins.

Sequences of retroviral origin occupy approximately 8% of the human genome. Most of these "retroviral" genes have lost their coding capacities since their entry into our ancestral genome millions of years ago, but some reading frames have remained open, suggesting positive selection. The complete sequencing of the human genome allowed a systematic search for retroviral envelope genes containing an open reading frame and resulted in the identification of 16 genes that we have characterized. We further showed, by quantitative reverse transcriptase PCR using specifically devised primers which discriminate between coding and noncoding elements, that all 16 genes are expressed in at least some healthy human tissues, albeit at highly different levels. All envelope genes disclose significant expression in the testis, three of them have a very high level of expression in the placenta, and a fourth is expressed in the thyroid. Besides their primary role as key molecules for viral entry, the envelope genes of retroviruses can induce cell-cell fusion, elicit immunosuppressive effects, and even protect against infection, and as such, endogenous retroviral envelope proteins have been tentatively identified in several reports as being involved in both normal and pathological processes. The present study provides a comprehensive survey of candidate genes and tools for a precise evaluation of their involvement in these processes.

Genes, env↗
PubMed2001

Attenuated lapinized chinese strain of classical swine fever virus: complete nucleotide sequence and character of 3'-noncoding region.

The complete nucleotide sequence including precise 5'- and 3'-terminal non-coding regions (NCRs) of the attenuated lapinized Chinese strain (HCLV) of Classical Swine Fever Virus (CSFV) was determined from overlapping cDNA clones constructed by separated RT-PCR and rapid amplification of cDNA ends (RACE) methods. The genomic RNA of the HCLV strain consists of 12.310 nucleotides (nts) including 374 nts and 242nts in the 5'- and 3'-NCRs, respectively. It contains one large open reading frame (ORF) encoding a polyprotein of 3,898 amino acids with a calculated molecular weight of 437.6 kDa. There is one notable insertion of 12 continuous nts, CTTTTTTCTTTT in the 3'-NCR of HCLV genomic cDNA when compared with its parental virulent Shimen strain. Sequence alignment of partial 3'-NCR reveals two groups of CSFV vaccine strains carrying similar T-rich insertions at different positions in this region. Computer-predicted secondary structures suggest that T-rich insertion greatly change the structures and thus decrease the promoter functions of 3'-NCRs during the replications of these two groups of CSFV vaccine strains.

3' Untranslated Regions↗
PubMed1996

Synthetic transcripts of double-stranded Birnavirus genome are infectious.

We have developed a system for generation of infectious bursal disease virus (IBDV), a segmented double-stranded RNA virus of the Birnaviridae family, with the use of synthetic transcripts derived from cloned cDNA. Independent full-length cDNA clones were constructed that contained the entire coding and noncoding regions of RNA segments A and B of two distinguishable IBDV strains of serotype I. Segment A encodes all of the structural (VP2, VP4, and VP3) and nonstructural (VP5) proteins, whereas segment B encodes the RNA-dependent RNA polymerase (VP1). Synthetic RNAs of both segments were produced by in vitro transcription of linearized plasmids with T7 RNA polymerase. Transfection of Vero cells with combined plus-sense transcripts of both segments generated infectious virus as early as 36 hr after transfection. The infectivity and specificity of the recovered chimeric virus was ascertained by the appearance of cytopathic effect in chicken embryo cells, by immunofluorescence staining of infected Vero cells with rabbit anti-IBDV serum, and by nucleotide sequence analysis of the recovered virus, respectively. In addition, transfectant viruses containing genetically tagged sequences in either segment A or segment B of IBDV were generated to confirm the feasibility of this system. The development of a reverse genetics system for double-stranded RNA viruses will greatly facilitate studies of the regulation of viral gene expression, pathogenesis, and design of a new generation of live vaccines.

Animals↗
PubMed1993

Genomic structure and promoter activity of the human testis lactate dehydrogenase gene.

The structure of the gene encoding the human testis-specific isozyme of lactate dehydrogenase (LDH) has been characterized and a regulatory region identified by promoter activity. The single-copy ldh-c gene has two alternative 5' noncoding exons and seven coding exons comprising an approximately 40-kb locus. The gene does not contain the canonical TATA or CAAT promoter sequences, and ribonuclease protection experiments suggest multiple transcription start sites. In the present study an immortalized murine germ cell line was used to detect promoter activity driven by 5' sequence of human ldh-c with lacZ as the reporter gene. Reporter gene activity was nondetectable when promoter constructs were transfected into nongerminal cells.

Animals↗
PubMed1999

Constructing primate phylogenies from ancient retrovirus sequences.

The genomes of modern humans are riddled with thousands of endogenous retroviruses (HERVs), the proviral remnants of ancient viral infections of the primate lineage. Most HERVs are nonfunctional, selectively neutral loci. This fact, coupled with their sheer abundance in primate genomes, makes HERVs ideal for exploitation as phylogenetic markers. Endogenous retroviruses (ERVs) provide phylogenetic information in two ways: (i) by comparison of integration site polymorphism and (ii) by orthologous comparison of evolving, proviral, nucleotide sequence. In this study, trees are constructed with the noncoding long terminal repeats (LTRs) of several ERV loci. Because the two LTRs of an ERV are identical at the time of integration but evolve independently, each ERV locus can provide two estimates of species phylogeny based on molecular evolution of the same ancestral sequence. Moreover, tree topology is highly sensitive to conversion events, allowing for easy detection of sequences involved in recombination as well as correction for such events. Although other animal species are rich in ERV sequences, the specific use of HERVs in this study allows comparison of trees to a well established phylogenetic standard, that of the Old World primates. HERVs, and by extension the ERVs of other species, constitute a unique and plentiful resource for studying the evolutionary history of the Retroviridae and their animal hosts.

Animals↗
PubMed1993

Organization and characterization of the rat class 3 aldehyde dehydrogenase gene.

Expression of class 3 aldehyde dehydrogenase (ALDH-3) is constitutive or inducible, depending on the tissue. ALDH-3 induction occurs both during neoplastic development and after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to study the regulation of ALDH-3 gene expression, ALDH-3 genomic sequences have been obtained from normal rat genomic DNA. Two overlapping genomic fragments (ALDH-UTR-1 and ALDH-NL2) contain the entire ALDH-3 gene along with considerable 5'- and 3'-flanking sequences. The rat ALDH-3 gene spans approximately 9 kilobases in length and consists of eleven exons; ten coding and one 5'-noncoding. The region 5' to exon one contains several putative transcription factor binding elements which may be important in the TCDD inducibility of this gene. These include a xenobiotic response element (XRE), a drug response element (DRE), LAP and Ap1 binding sites, and one Sp1 site. There are considerable differences in organization between the rat and human class 3 ALDH genes. Primer extension and RNase protection analysis indicate that both basal and TCDD-inducible expression of the ALDH-3 gene utilize the same multiple transcription start sites.

Aldehyde Dehydrogenase↗
PubMed1981

Sequence heterogeneity, multiplicity, and genomic organization of alpha- and beta-tubulin genes in sea urchins.

We analyzed the multiplicity, heterogeneity, and organization of the genes encoding the alpha and beta tubulins in the sea urchin Lytechinus pictus by using cloned complementary deoxyribonucleic acid (cDNA) and genomic tubulin sequences. cDNA clones were constructed by using immature spermatogenic testis polyadenylic acid-containing ribonucleic acid as a template. alpha- and beta-tubulin clones were identified by hybrid selection and in vitro translation of the corresponding messenger ribonucleic acids, followed by immunoprecipitation and two-dimensional gel electrophoresis of the translation products. The alpha cDNA clone contains a sequence that encodes the 48 C-terminal amino acids of alpha tubulin and 104 base pairs of the 3' nontranslated portion of the messenger ribonucleic acid. The beta cDNA insertion contains the coding sequence for the 100-C terminal amino acids of beta tubulin and 83 pairs of the 3' noncoding sequence. Hybrid selections performed at different criteria demonstrated the presence of several heterogeneous, closely related tubulin messenger ribonucleic acids, suggesting the existence of heterogeneous alpha- and beta-tubulin genes. Hybridization analyses indicated that there are at least 9 to 13 sequences for each of the two tubulin gene families per haploid genome. Hybridization of the cDNA probes to both total genomic DNA and cloned germline DNA fragments gave no evidence for close physical linkage of alpha-tubulin genes with beta-tubulin genes at the DNA level. In contrast, these experiments indicated that some genes within the same family are clustered.

Animals↗
PubMed1998

Loss of imprinting of igf2 in renal-cell carcinomas.

Loss of imprinting (LOI) of the igf2 and h19 genes has been found not only in embryonal tumors but also in common adult cancers. To determine any possible role of genomic imprinting in the development of renal-cell carcinomas (RCCs), we examined the imprinting status of igf2 and h19 in a series of 22 such tumors, and studied its relation to their mRNA expression. Of 14 RCC specimens heterozygous for the ApaI polypmorphism, 7 (50%) showed LOI of igf2. In contrast, for h19 all 9 informative cases maintained imprinting. Furthermore, all 7 cases with LOI transcribed igf2 mRNA at elevated levels, while H19 expression was low regardless of the imprinting status compared with that of background level in each case. These results suggest that LOI of igf2, but not of h19, plays a role in the case of human RCC. However, in contrast to that in Wilms' tumor, LOI in RCC was not associated with any specific down-regulation of h19.

Adult↗
PubMed1997

Genomic imprinting in the rat: linkage of Igf2 and H19 genes and opposite parental allele-specific expression during embryogenesis.

Igf2 and H19 are closely linked imprinted genes in both mice and humans that are expressed from opposite parental alleles. In this study we demonstrate that these two genes are also closely linked in the rat, with the H19 gene mapping to within 145 kb of Igf2 on rat chromosome 1. We identified polymorphisms in H19 and Igf2 transcripts in two inbred rat strains and determined the expression of the parental alleles in F1 offspring. The H19 gene was shown to be expressed exclusively from the maternal allele in all fetal and neonatal tissues. Monoallelic expression of Igf2 from the paternal allele was found in all tissues except the leptomeninges and choroid plexus. Igf2 in the choroid plexus was monoallelic at days 13.5 and 15.5 of gestation with a switch to biallelic expression by day 18.5, demonstrating a loss of imprinting after the choroid plexus has differentiated. Biallelic expression of Igf2 was observed in the leptomeninges at all fetal and neonatal stages analyzed. These studies demonstrate conservation of imprinting of two closely linked genes transcribed from opposite parental alleles in a species other than human or mouse. A comparative approach between different species will be important in defining the mechanisms that regulate the tissue-specific expression of imprinted genes.

Alleles↗
PubMed1998

Genomic imprinting in ruminants: allele-specific gene expression in parthenogenetic sheep.

Studies in the mouse have established that both parental genomes are essential for normal embryonic development. Parthenogenetic mouse embryos (which have two maternal genomes and no paternal genome), for example, are growth-retarded and die at early postimplantation stages. The distinct maternal and paternal contributions are mediated by genomic imprinting, an epigenetic mechanism by which the expression of certain genes is dependent on whether they are inherited from mother or father. Although comparative studies have established that many imprinted mouse (and rat) genes are allele-specifically expressed in humans as well (and vice versa), so far imprinting studies have not been performed in other mammalian species. When considering evolutionary theories of genomic imprinting, it would be important to know how widely it is conserved among placental mammals. We have investigated its conservation in a bovid ruminant, the domestic sheep, by comparing parthenogenetic and normal control embryos. Our study establishes that, like in the mouse, parthenogenetic development in sheep is associated with growth-retardation and does not proceed beyond early fetal stages. These developmental abnormalities are most likely caused by imprinted genes. We demonstrate that, indeed, like in mice and humans, the growth-related PEG1/MEST and Insulin-like Growth Factor 2 (IGF2) genes are expressed from the paternal chromosome in sheep. These observations suggest that genomic imprinting is conserved in a third, evolutionarily rather diverged group of placental mammals, the ruminants.

Alleles↗
PubMed1990

Chromosomal reallocation of the chicken c-myb locus and organization of 3'-proximal coding exons.

In the course of our studies concerning the tissue-specific expression of the c-myb proto-oncogene, we have established the nucleotide sequence of the chicken c-myb 3'-proximal coding exons. In situ hybridization performed with different genomic DNA probes corresponding to nearly all the c-myb gene allowed us to localize the corresponding locus on the large acrocentric chromosome 3 in chicken. Our sequencing data also indicate that the 3'-proximal noncoding sequences represented in c-myb mRNA species are derived from non-contiguous exons.

Animals↗
PubMed1986

Characterization of a ribosomal DNA clone of Brugia malayi.

The structure of ribosomal DNA (rDNA) clone pBmr7 from microfilariae of the human parasite Brugia malayi has been examined in detail by Southern blot analysis and S-1 mapping techniques. The results demonstrate that this clone contains regions homologous to 28S, 18S and 5.8S rDNAs. A noncoding or 'spacer' region lies between the 3' end of 28S rDNA and the 5' end of 18S rDNA. An AccI-Sau3AI fragment of approximately 900 bp from this spacer region cross-hybridizes to genomic DNA fragments of different sizes from Brugia pahangi and Dirofilaria immitis. The differences observed in hybridization suggest that this rDNA fragment can be used to differentiate between various filariid species.

Animals↗
PubMed2004

Detailed mapping of the ERG-ETS2 interval of human chromosome 21 and comparison with the region of conserved synteny on mouse chromosome 16.

We have carried out a detailed annotation of 550 kb of genomic DNA on human chromosome 21 containing the ERG and ETS2 genes. Comparative genomic analysis between this region and the interval of conserved synteny on mouse chromosome 16 indicated that the order and orientation of the ERG and ETS2 genes were conserved and revealed several regions containing potential conserved noncoding sequences. Four pseudogenes including those for small protein G, laminin receptor, human transposase protein and meningioma-expressed antigen were identified. A potentially novel gene (C21orf24) with alternative mRNA transcripts, consensus splice donor and acceptor sites, but no coding potential nor murine orthologue, was identified and found to be expressed in a range of human cell lines. We have identified four novel splice variants that arise from a previously undescribed 5' exon of the human ERG gene. Comparison of the cDNA sequences enabled us to determine the complete exon-intron structure of the ERG gene. We have also identified the presence of noncoding RNAs in the first and second introns of the ETS2 gene. Our studies have important implications for Down syndrome as this region contains multiple mRNA transcripts, both coding and potentially noncoding, that may play as yet undescribed roles in the pathogenesis of this disorder.

Alternative Splicing↗