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At least 1,063 records · Page 59Linked to original sources
PubMed2026

Overexpression of a subset of long intergenic noncoding RNAs in uterine serous carcinoma predicts poor prognosis.

The evaluation and prediction of uterine serous carcinoma (USC), a type of endometrial cancer that is more severe than endometrioid adenocarcinoma, remain challenging. Long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers. This study assessed the expression patterns and prognostic values of long intergenic noncoding RNAs (lincRNAs) in USC. RNA sequencing, copy number variation (CNV), and clinical data from The Cancer Genome Atlas were used to investigate various lncRNAs in endometrial cancer. LincRNAs, a major subclass of lncRNAs, exhibit specific expression patterns modulated by CNVs and act as predictors of poor prognosis, survival, and recurrence in USC. Functional analyses were conducted to investigate the roles of lncRNAs in USC. Finally, the expression of these lincRNAs was verified in 32 pairs of USCs collected from the hospital over 3 years. A series of lincRNAs were found to be specifically expressed in USC compared with other lncRNAs and regulated by CNV. Moreover, these specific upregulated lincRNAs, particularly ENSG00000281406, ENSG00000226791, ENSG00000269903, and ENSG00000204277, demonstrated poor prognoses for survival and recurrence in USC. Functionally, our analysis showed that ENSG00000281406 positively correlated with the Wnt signaling pathway, whereas ENSG00000226791, ENSG00000269903, and ENSG00000204277 negatively correlated with the T-cell receptor signaling pathway. Importantly, we confirmed that ENSG00000204277 negatively correlated with CD8+ T-cell immune infiltration in USC. Our results highlight that these lincRNAs can serve as new biomarkers for the prognostic prediction of USC. In particular, ENSG00000204277 may be used as a therapeutic target for USC.

Humans↗
PubMed1988

Sequence and structure at the genome 3' end of the U2-strain of tobacco mosaic virus, a histidine-accepting tobamovirus.

The primary sequence of the 3' noncoding region of U2-TMV RNA was determined. A structural model was proposed based on chemical and enzymatic structure mapping as well as on analyses of nuclease protection by aminoacyl-tRNA-synthetase. The model agrees with those proposed for TMV "vulgare" RNA and confirms their general validity for the tobamoviruses. The RNA appears to have a tRNA-like, L-shaped structure at the 3' terminus, linked to a quasi-continuous double-helical stalk, with five pseudoknots involved in the formation of the whole structure. However, the structure of U2-TMV RNA is less stringently conserved than the 3' termini of "vulgare" and other histidine-accepting tobamoviruses. This difference is reflected in the kinetics of aminoacylation of the RNA.

Base Sequence↗
PubMed1982

Cytochrome c gene-related sequences in mammalian genomes.

We use a rat cytochrome c gene that we previously isolated and determined the sequence of to estimate the number of related sequences present in the rat genome. Approximately 25 different EcoRI restriction endonuclease fragments from total rat DNA hybridize to the gene of known structure. Four of these correspond to homologous sequences present in four different lambda Charon 4A-rat cytochrome c recombinants previously isolated. Intact or nearly intact genes appear to reside on almost all of the genomic fragments, because they hybridize strongly to gene subfragments representing both 5' and 3' portions of the coding sequence as well as to 3' noncoding DNA that is found specifically associated with the coding region. A subgroup of about six of the fragments also shares homology within the 73 nucleotides immediately preceding the AUG codon. An intron-specific probe reveals only the EcoRI fragment from which it was derived and one other genomic fragment. On the basis of the temperature of complete dissociation of the coding region probe in 0.75 M NaCl/0.075 M Na3 citrate/50% (vol/vol) formamide, the 25 fragments are separable into three stringency classes of 40-50 degrees C, 50-55 degrees C, and 55-60 degrees C. The latter, high-stringency group of about seven fragments includes those cloned in the recombinant phage isolates, whose regions homologous to cytochrome c are shown to differ from the purified gene of known sequence by an amount equivalent to about 2% mismatched bases. Families of cytochrome c gene-related sequences are also found in the genomes of several other mammals, including humans.

Animals↗
PubMed1992

Reversion of Q beta RNA phage mutants by homologous RNA recombination.

Q beta phage RNAs with inactivating insertion (8-base) or deletion (17-base) mutations within their replicase genes were prepared from modified Q beta cDNAs and transfected into Escherichia coli spheroplasts containing Q beta replicase provided in trans by a resident plasmid. Replicase-defective (Rep-) Q beta phage produced by these spheroplasts were detected as normal-sized plaques on lawns of cells containing plasmid-derived Q beta replicase, but were unable to form plaques on cells lacking this plasmid. When individual Rep- phage were isolated and grown to high titer in cells containing plasmid-derived Q beta replicase, revertant (Rep+) Q beta phage were obtained at a frequency of ca. 10(-8). To investigate the mechanism of this reversion, a point mutation was placed into the plasmid-derived Q beta replicase gene by site-directed mutagenesis. Q beta mutants amplified on cells containing the resultant plasmid also yielded Rep+ revertants. Genomic RNA was isolated from several of the latter phage revertants and sequenced. Results showed that the original mutation (insertion or deletion) was no longer present in the phage revertants but that the marker mutation placed into the plasmid was now present in the genomic RNAs, indicating that recombination was one mechanism involved in the reversion of the Q beta mutants. Further experiments demonstrated that the 3' noncoding region of the plasmid-derived replicase gene was necessary for the reversion-recombination of the deletion mutant, whereas this region was not required for reversion or recombination of the insertion mutant. Results are discussed in terms of a template-switching model of RNA recombination involving Q beta replicase, the mutant phage genome, and plasmid-derived replicase mRNA.

Amino Acid Sequence↗
PubMed1989

[Molecular genetic analysis of poliovirus infection].

Molecular genetic studies of the antigenicity and the attenuation phenotype of type 1 poliovirus were described. Antigenic sites were identified on the genome of type 1 poliovirus by the determination of nucleotide sequence of the genome of variants that were not neutralized by the neutralizing monoclonal antibodies. The solution of the crystal structure of poliovirus revealed that all mutations found as above are located at the surface of the virion and cluster into three distinct sites. These regions probably represent distinct antibody binding sites. To study expression of the attenuation phenotype of type 1 poliovirus, a number of recombinant polioviruses were constructed in vitro by using infectious complementary deoxyribonucleic acid clones of the virulent Mahoney and attenuated Sabin 1 strains of type 1 poliovirus. Biological tests including a monkey neurovirulence test were performed on the recombinants. The results indicated that the 5' noncoding region harbors a relatively strong determinant influencing the attenuation. Further studies revealed that an adenine residue (Mahoney type) at nucleotide position 480 importantly contribute to the expression of the neurovirulence phenotype. However, a guanine residue (Sabin 1 type) at position 480 was not sufficient for full expression of the attenuation phenotype encoded by this genome region. These results suggested that the expression of the attenuation phenotype depends on the highly ordered structure formed in the 5' noncoding sequence and that the formation of such a structure is possibly influenced by the nucleotide position 480. To investigate the structure and function of the 5' noncoding region, many insertion and deletion sequences were introduced into the genome region. Replication processes of the mutants were analysed and second-site mutations in the genome of the variants that partially restored the phenotypes of the parental viruses were identified. The results indicated that interactions between different loci, for example at around positions 200 and 500, are important for maintaining the viral replication efficiency.

Animals↗
PubMed1992

The small genome of Arabidopsis contains at least six expressed alpha-tubulin genes.

The goal of our investigations is to define the genetic control of microtubule-based processes in a higher plant. The available evidence suggests that we have achieved our first objective: the characterization of the complete alpha-tubulin and beta-tubulin gene families of Arabidopsis. Four additional alpha-tubulin genes (TUA2, TUA4, TUA5, and TUA6) of Arabidopsis have been cloned and sequenced to complete the analysis of the gene structure for all six alpha-tubulin genes detectable on DNA gel blots of Arabidopsis genomic DNA hybridized with alpha-tubulin coding sequences. TUA1 and TUA3 were characterized earlier in our laboratory. Noncoding gene-specific hybridization probes have been constructed for all six alpha-tubulin genes and used in RNA gel blot analyses to demonstrate that all six genes are transcribed. The six genes encode four different alpha-tubulin isoforms; TUA2 and TUA4 encode a single isoform, as do TUA3 and TUA5. Two-dimensional protein gel immunoblot analyses have resolved at least four alpha-tubulin isoforms from plant tissues, suggesting that all of the predicted TUA gene products are synthesized in vivo.

Amino Acid Sequence↗
PubMed1996

The mitochondrial genome of a monotreme--the platypus (Ornithorhynchus anatinus).

The complete nucleotide sequence of the mitochondrial genome of a platypus (Ornithorhynchus anatinus) was determined. Its overall genomic organization is similar to that of placental mammals, Xenopus laevis, and fishes. However, it contains an apparently noncoding sequence of 88 base pairs located between the genes for tRNA(Leu)(UUR) and ND1. The base composition of this sequence and its conservation among monotremes, as well as the existence of a transcript from one of the strands, indicate that it may have a hitherto-unknown function. When the protein-coding sequences are used to reconstruct a phylogeny of mammals, the data suggest that monotremes and marsupials are sister groups and thus that placental mammals represent the most ancient divergence among mammals.

Animals↗
PubMed2004

Genomic heterogeneity of background substitutional patterns in Drosophila melanogaster.

Mutation is the underlying force that provides the variation upon which evolutionary forces can act. It is important to understand how mutation rates vary within genomes and how the probabilities of fixation of new mutations vary as well. If substitutional processes across the genome are heterogeneous, then examining patterns of coding sequence evolution without taking these underlying variations into account may be misleading. Here we present the first rigorous test of substitution rate heterogeneity in the Drosophila melanogaster genome using almost 1500 nonfunctional fragments of the transposable element DNAREP1_DM. Not only do our analyses suggest that substitutional patterns in heterochromatic and euchromatic sequences are different, but also they provide support in favor of a recombination-associated substitutional bias toward G and C in this species. The magnitude of this bias is entirely sufficient to explain recombination-associated patterns of codon usage on the autosomes of the D. melanogaster genome. We also document a bias toward lower GC content in the pattern of small insertions and deletions (indels). In addition, the GC content of noncoding DNA in Drosophila is higher than would be predicted on the basis of the pattern of nucleotide substitutions and small indels. However, we argue that the fast turnover of noncoding sequences in Drosophila makes it difficult to assess the importance of the GC biases in nucleotide substitutions and small indels in shaping the base composition of noncoding sequences.

Animals↗
PubMed2002

[Variation of the mitochondrial genome in the evolution of Drosophila].

The evidence on mitochondrial genome variation and its role in evolution of the genus Drosophila are reviewed. The mitochondrial genome is represented by a circular double-stranded DNA molecule 16 to 19 kb in length. The genome contains no introns involved in recombination. The entire mitochondrial genome can be arbitrarily divided into three parts: (1) protein-coding genes; (2) genes encoding rRNA and tRNA; and (3) the noncoding regulatory region (A + T region). The selective importance of mutations within different mtDNA regions is therefore unequal. In Drosophila, the content of the A + T pairs in mtDNA is extremely low and a pattern of nucleotide substitution is characterized by a low transition/transversion ratio (and a low threshold of mutation saturation). The deletions and duplications are of common occurrence in the mitochondrial genome. However, this genome lacks such characteristic for the nuclear genome aberrations as the inversions and transpositions. The phenomena of introgression and heteroplasmy provide an opportunity to study the adaptive role of the mitochondrial genome and its role in speciation. Analysis of evidence concerning mtDNA variation in different species of the genus Drosophila made it possible to ascertain data on phylogenetic relationships among species obtained by studying nuclear genome variation. In some species, mtDNA variation may serve as a reliable marker for population differentiation within a species, although evidence on the population dynamics of the mtDNA variation is very scarce.

Animals↗
PubMed1993

Differential expression of six glutamine synthetase genes in Zea mays.

The maize genome has been shown to contain six glutamine synthetase (GS) genes with at least four different expression patterns. Noncoding 3' gene-specific probes were constructed from all six GS cDNA clones and used to examine transcript levels in selected organs by RNA gel blot hybridization experiments. The transcript of the single putative chloroplastic GS2 gene was found to accumulate primarily in green tissues, whereas the transcripts of the five putative GS1 genes were shown to accumulate preferentially in roots. The specific patterns of transcript accumulation were quite distinct for the five GS1 genes, with the exception of two closely related genes.

Cell Compartmentation↗
PubMed2003

Mammalian mutation pressure, synonymous codon choice, and mRNA degradation.

The usage of synonymous codons (SCs) in mammalian genes is highly correlated with local base composition and is therefore thought to be determined by mutation pressure. The usage is nonetheless structured. For instance, mammals share with Saccharomyces and Drosophila most preferences for the C-ending over the G-ending codon (or vice versa) within each fourfold-degenerate SC family and the fact that their SCs are placed along coding regions in ways that minimize the number of T|A and C|G dinucleotides ("|" being the codon boundary). TA and CG underrepresentations are observed everywhere in the mammalian genome affecting the SC usage, the amino acid composition of proteins, and the primary structure of introns and noncoding DNA. While the rarity of CG is ascribed to the high mutability of this dinucleotide, the rarity of TA in coding regions is considered adaptive because UA dinucleotides are cleaved by endoribonucleases. Here we present in vivo experimental evidence indicating that the number of T|A and/or C|G dinucleotides of a human gene can affect strongly the expression level and degradation of its mRNA. Our results are consistent with indirect evidence produced by other workers and with the detailed work that has been devoted to characterize UA cleavage in vitro and in vivo. We conclude that SC choice can influence strongly mRNA function and gene expression through effects not directly related to the codon-anticodon interaction. These effects should constrain heavily the nucleotide motif composition of the most abundant mRNAs in the transcriptome, in particular, their SC usage, a usage that must be reflected by cellular tRNA concentrations and thus defines for all other genes which SCs are translated fastest and most accurately. Furthermore, the need to avoid such effects genome-wide appears serious enough to have favored the evolution of biases in context-dependent mutation that reduce the occurrence of intrinsically unfavorable motifs, and/or, when possible, to have induced the molecular machinery mediating such effects to rely opportunistically on already existing motif rarities and abundances. This may explain why nucleotide motif preferences are very similar in transcribed and nontranscribed mammalian DNA even though the preferences appear to be adaptive only in transcribed DNA.

Animals↗
PubMed1993

Generalized Lévy-walk model for DNA nucleotide sequences.

We propose a generalized Lévy walk to model fractal landscapes observed in noncoding DNA sequences. We find that this model provides a very close approximation to the empirical data and explains a number of statistical properties of genomic DNA sequences such as the distribution of strand-biased regions (those with an excess of one type of nucleotide) as well as local changes in the slope of the correlation exponent alpha. The generalized Lévy-walk model simultaneously accounts for the long-range correlations in noncoding DNA sequences and for the apparently paradoxical finding of long subregions of biased random walks (length lj) within these correlated sequences. In the generalized Lévy-walk model, the lj are chosen from a power-law distribution P(lj) varies as lj(-mu). The correlation exponent alpha is related to mu through alpha = 2-mu/2 if 2 < mu < 3. The model is consistent with the finding of "repetitive elements" of variable length interspersed within noncoding DNA.

Base Sequence↗
PubMed2004

Subfunction partitioning, the teleost radiation and the annotation of the human genome.

Half of all vertebrate species are teleost fish. What accounts for this explosion of biodiversity? Recent evidence and advances in evolutionary theory suggest that genomic features could have played a significant role in the teleost radiation. This review examines evidence for an ancient whole-genome duplication (tetraploidization) event that probably occurred just before the teleost radiation. The partitioning of ancestral subfunctions between gene copies arising from this duplication could have contributed to the genetic isolation of populations, to lineage-specific diversification of developmental programs, and ultimately to phenotypic variation among teleost fish. Beyond its importance for understanding mechanisms that generate biodiversity, the partitioning of subfunctions between teleost co-orthologs of human genes can facilitate the identification of tissue-specific conserved noncoding regions and can simplify the analysis of ancestral gene functions obscured by pleiotropy or haploinsufficiency. Applying these principles on a genomic scale can accelerate the functional annotation of the human genome and understanding of the roles of human genes in health and disease.

Animals↗
PubMed1992

Application of genome sequence information in potyvirus taxonomy: an overview.

The application of protein and nucleic acid sequence analysis in evolutionary and phylogenetic studies is well established. Available sequence information for the 5' untranslated region of potyviruses including the fungus-transmitted barley yellow mosaic virus (BaYMV) RNA-1 suggests that a 12-nucleotide conserved sequence, the "potybox" is unique to this group. Various non-structural proteins of potyviruses share considerable "signature" sequence homology across a broad spectrum of unrelated viruses, which makes their value limited to "supergroup" or "superfamily" identity. However, in potyviruses, the coat-protein N-terminal sequences and 3' noncoding regions are variable among viruses, but similar among strains of the same virus. This suggests that these sequences may be an accurate marker of genetic relatedness. Until complete genome sequences from a large number of potyviruses become available and their value in systematics is tested, coat protein and 3' noncoding regions remain as the choice of taxonomic indicators. The reason being, that cloning and sequencing of the coat-protein gene and 3' noncoding regions are less complicated and time consuming and the sequences show significant differences among the virus species within the family Potyviridae.

Animals↗
PubMed1990

Nucleotide sequences and novel structural features of human and Chinese hamster hsp60 (chaperonin) gene families.

A number of clones that specifically hybridize to the human hsp60 cDNA (chaperonin protein; GroEL homolog) were isolated from human and Chinese hamster ovary cell genomic libraries. DNA sequence analysis shows that one of these clones, pGem-10, is completely homologous to the human hsp60 cDNA (in both coding and noncoding regions) with no intervening sequences. The other human clones analyzed were all nonfunctional pseudogenes containing numerous small additions, deletions, and base substitutions, but no introns. On the basis of sequence data, six different hsp60 pseudogenes were identified in human cells. In addition, we also cloned and completely sequenced a genomic clone from CHO cells. This clone, which was also a pseudogene, contained a small 87-nucleotide intron near the 3' end. Southern blot analysis of human, mouse, and Chinese hamster DNA, digested with unique restriction enzymes (no sites in cDNA), indicates the presence of about 8-12 genes for hsp60 in the vertebrate genomes. The sequence data, however, suggest that most of these genes, except one (per haploid genome), are likely to be nonfunctional pseudogenes.

Animals↗
PubMed2006

Pre-messenger RNA processing and its regulation: a genomic perspective.

The sequence of entire genomes from higher eukaryotes revealed that an average gene is very large due to the interruption of the coding sequence with large noncoding introns. Introns are co-transcriptionally removed by splicing with great accuracy and fidelity, although contrary to our expectations, currently known signals required for pre-messenger RNA (mRNA) processing are very degenerate and redundant. Furthermore, the vast majority of genes are alternatively processed. A large number of proteins are therefore involved in generating specificity in pre-mRNA processing that requires a dedicated mechanisms to operate at genomic dimensions. In this review I will summarize recent progress in understanding how established principles of pre-mRNA processing extend to genomic dimensions and discuss emerging concepts in coupling of pre-mRNA processing with other nuclear events and nuclear organization.

Alternative Splicing↗
PubMed2005

Molecular mechanisms of extensive mitochondrial gene rearrangement in plethodontid salamanders.

Extensive gene rearrangement is reported in the mitochondrial genomes of lungless salamanders (Plethodontidae). In each genome with a novel gene order, there is evidence that the rearrangement was mediated by duplication of part of the mitochondrial genome, including the presence of both pseudogenes and additional, presumably functional, copies of duplicated genes. All rearrangement-mediating duplications include either the origin of light-strand replication and the nearby tRNA genes or the regions flanking the origin of heavy-strand replication. The latter regions comprise nad6, trnE, cob, trnT, an intergenic spacer between trnT and trnP and, in some genomes, trnP, the control region, trnF, rrnS, trnV, rrnL, trnL1, and nad1. In some cases, two copies of duplicated genes, presumptive regulatory regions, and/or sequences with no assignable function have been retained in the genome following the initial duplication; in other genomes, only one of the duplicated copies has been retained. Both tandem and nontandem duplications are present in these genomes, suggesting different duplication mechanisms. In some of these mitochondrial DNAs, up to 25% of the total length is composed of tandem duplications of noncoding sequence that includes putative regulatory regions and/or pseudogenes of tRNAs and protein-coding genes along with the otherwise unassignable sequences. These data indicate that imprecise initiation and termination of replication, slipped-strand mispairing, and intramolecular recombination may all have played a role in generating repeats during the evolutionary history of plethodontid mitochondrial genomes.

Animals↗
PubMed2003

The nature of diversity and diversification at the ABO locus.

In this study we analyzed the complete genomic sequences, except intron 1, and 2 regulatory regions of 6 common (ABO*A101, ABO*A201, ABO*B101, ABO*O01, ABO*O02, and ABO*O03) and 18 rare ABO alleles, 3 of which were new. This was done by phylogenetic analysis and correlating sequence data with the ABO phenotypes. The study revealed multiple polymorphisms in noncoding regions. The intron-based phylogenetic analysis revealed 5 main lineages: ABO*A, ABO*B, ABO*O01, ABO*O02, and ABO*O03. The genomic sequences of most rare ABO alleles differed slightly from those of the common alleles. Singular mutations or hybrid alleles were most common, but a few exhibited mosaic sequence pattern containing multiple exon and/or intron motifs from other ABO lineages. Thus, both an accumulation of mutations as well as an assortment of the mutations by recombination seems to be responsible for the ABO gene diversity. The prevalence of replacement mutations indicates positive selection for allelic diversity. Phenotype-genotype correlation showed that sequence variations within the complete coding sequence can affect A- and B-antigen expression. All variant ABO*A/B alleles and one new ABO*O03-like allele were associated with weak ABO phenotypes. These findings are suggestive of the requirement of a comprehensive coding sequence database for sequence-based phenotype prediction.

ABO Blood-Group System↗