Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During differentiation of mouse 3T3-L1 fibroblasts to an adipocyte phenotype, the mitochondrial isoform of aspartate aminotransferase accumulates on the plasma membrane. The determination of whether this reflects translation of an alternatively spliced message lacking the mitochondrial leader sequence required cloning of the enzyme's uncommon a allele, for which these cells are homozygous. The 1.4-kb cDNA sequence of the a allele was obtained from oligo-dT-primed reverse-transcriptase PCR products amplified from FVB mouse RNA. It differed from the b allele at only 2 bp and one amino acid. By contrast, gene-specific primers generated an additional 1.4-kb fragment that differed from the b allele by approximately 1% of nucleotides, encoding four amino acid substitutions. This sequence proved to represent a recently diverged processed pseudogene. The presence of such pseudogenes can complicate interpretation of expressed-sequence-tag data and single-nucleotide-polymorphism genotyping studies. Using probes derived from the a allele, RNase protection analyses indicated that only a single message for the enzyme was present in 3T3-L1 fibroblasts and adipocytes, despite differences in subcellular protein distribution.
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PMID:Mitochondrial aspartate aminotransferase: direction of a single protein with two distinct functions to two subcellular sites does not require alternative splicing of the mRNA. 1064 97

Phylogenetic analyses of secretory ribonucleases or RNases 1 have shown that gene duplication events, giving rise to three paralogous genes (pancreatic, seminal and brain RNase), occurred during the evolution of ancestral ruminants. A higher number of paralogous sequences are present in chevrotain (Tragulus javanicus), the earliest diverged taxon within the ruminants. Two pancreatic RNase sequences were identified, one encoding the pancreatic enzyme, the other encoding a pseudogene. The identity of the pancreatic enzyme was confirmed by isolation of the protein and N-terminal sequence analysis. It is the most acidic pancreatic ribonuclease identified so far. Formation of the mature enzyme requires cleavage by signal peptidase of a peptide bond between two glutamic acid residues. The seminal-type RNase gene shows features of a pseudogene, like orthologous genes in other ruminants investigated with the exception of the bovine species. The brain-type RNase gene of chevrotain is expressed in brain tissue. A hybrid gene with a pancreatic-type N-terminal and a brain-type C-terminal sequence has been identified but nothing is known about its expression. Phylogenetic analysis of RNase 1 sequences of six ruminant, three other artiodactyl and two whale species support previous findings that two gene duplications occurred in a ruminant ancestor. Three distinct groups of pancreatic, seminal-type and brain-type RNases have been identified and within each group the chevrotain sequence it the first to diverge. In taxa with duplications of the RNase gene (ruminants and camels) the gene evolved at twice as fast than in taxa in which only one gene could be demonstrated; in ruminants there was an approximately fourfold increase directly after the duplications and then a slowing in evolutionary rate.
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PMID:Secretory ribonucleases in the primitive ruminant chevrotain (Tragulus javanicus). 1145 81

Mammalian pancreatic-type ribonucleases (RNases) 1 represent single-copy genes in the genome of most investigated mammalian species, including Mus musculus and other murid rodents. However, in six species belonging to the genus Rattus and closely related taxa, several paralogous gene products were identified by Southern blotting and PCR amplifications of genomic sequences. Phylogenies of nucleotide and derived amino acid sequences were reconstructed by several procedures, with three Mus species as outgroup. Duplications of the RNase 1 occurred after the divergence of Niviventer cremoriventer and Leopoldamys edwardsi from the other investigated species. Four groups of paralogous genes could be identified from specific amino acid sequence features in each of them. Low ratios of nonsynonymous-to-synonymous substitutions and the paucity of pseudogene features suggest functional gene products. One of the RNase 1 genes of R. norvegicus is expressed in the pancreas. RNases 1 were isolated from pancreatic tissues of R. rattus and R. exulans and submitted to N-terminal amino acid sequence analysis. In R. rattus, the orthologue of the expressed gene of R. norvegicus was identified, but in R. exulans, two paralogous gene products were found. The gene encoding for one of these had not yet been found by PCR amplification of genomic DNA. A well-defined group of orthologous sequences found in five investigated species codes for very basic RNases. Northern blot analysis showed expression of messenger RNA for this RNase in the spleen of R. norvegicus, but the protein product could not be identified. Evolutionary rates of RNase 1, expressed as nucleotide substitutions per site per 10(3) million years (Myr), vary between 5 and 9 in the lines leading to Mus, Niviventer, and Lepoldamys (on the basis of an ancestral date of mouse/rat divergence of 12.2 Myr) and between 20 and 50 in the lines to the other sequences after divergence from Niviventer and Leopoldamys (5.5 Myr).
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PMID:Pancreatic-type ribonuclease 1 gene duplications in rat species. 1239 26

The syndecan family of heparan sulfate proteoglycans participates in cellular activation through interactions with growth factors, extracellular matrix, and other molecules. The family consists of four proteins that share sequence homology within their cytosolic domains. Here we report that a 5.8 kb region of human chromosome 22q12.2 contains multiple segments that share greater than 80% sequence homology to the syndecan 4 transcript, including homology to 443 nucleotides of the syndecan 4 coding region. Three pieces of evidence indicate that the chromosome 22 sequences are a syndecan 4 pseudogene. First, single nucleotide gaps need to be inserted into the chromosome 22 sequence in order to maintain maximal alignment to the syndecan 4 coding sequence, and this introduces stop codons into a deduced amino acid sequence. Second, the total length of chromosome 22 containing the homologous sequences is compressed when compared to the genomic organization of the complementary syndecan 4 sequences. Third, the 5.8 kb chromosome 22 sequence contains multiple Alu and other repetitive sequences, and this is a property of pseudogenes. Both RT-PCR and RNase protection assays indicated that the syndecan 4 pseudogene is transcribed in human umbilical vein endothelial cells.
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PMID:Identification of a syndecan 4 pseudogene. 1265 6

Mice and rats are naturally deficient in cholesteryl ester transfer protein (CETP) activity, although the reason behind the deficiency in activity is unknown. A search of mouse genome databases revealed sequences resembling 7 of the 16 human exons. However, these sequences could not code for a functional CETP. Analysis of the rat genome using Southern blotting revealed sequences complementary to human CETP cDNA, but RNase protection assays were unable to detect any Cetp gene expression in liver, adipose, or muscle. A search of rat whole-genome shotgun databases revealed exon-like sequences that would be unable to code for a functional CETP. An Ap3s1 pseudogene lay immediately upstream of the CETP-like sequences in mouse, but was nearly identical to the functional gene and unlikely to have been inserted prior to mouse-rat divergence. In contrast, a deletion leading to a nonsense codon was found in the exon 11-like sequences of both rat and mouse and not in any other species. Thus, the lack of CETP activity in both the mouse and the rat is most likely due to an evolutionary event that occurred before these species diverged and not to altered regulation of the gene or function of the gene product.
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PMID:Genomic evidence for the absence of a functional cholesteryl ester transfer protein gene in mice and rats. 1279 33

The eukaryotic trifunctional enzyme, C(1)-tetrahydrofolate (THF) synthase, interconverts folic acid derivatives between various oxidation states and is critical for normal cellular function, growth, and differentiation. Using a rat C(1)-THF synthase cDNA and synthetic oligonucleotides, the rat C(1)-THF synthase gene was isolated and characterized. The gene consists of 28 exons and spans 67.5 kbp. Primer extension, RNase protection, and rapid amplification of cDNA ends (RACE) experiments indicate the presence of multiple transcription start points (tsp) within a 250-bp window located between 50 and 300 bp upstream from the start codon. The 5' flanking region is devoid of a TATA consensus sequence motif, but putative regulatory elements, including NF-kappabeta, HNF-4alpha1, RARalpha1, C/EBP, and PPAR are present in the promoter region. The 5' flanking region also contains two sets of tetranucleotide repeats and two short interspersed nuclear elements (SINES). The initial 2500 bp of 5' flanking sequences of the rat and mouse cytoplasmic C(1)-THF synthase genes share 70% identity. However, comparison with the human gene from the Human Genome Data Bank revealed no significant homology in the 5' flanking region. The gene structure characterization led to the identification of a pseudogene that is 94% identical to the C(1)-THF synthase gene and probably diverged 10-12 million years ago. In addition, the gene expression patterns of C(1)-THF synthase were investigated during liver regeneration and liver and kidney organogenesis, two highly regulated events. In both processes, C(1)-THF synthase expression correlated with increased nucleotide metabolism. This pattern suggests that the gene is regulated in response to changes in the demand for folate-dependent one-carbon units.
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PMID:Characterization of the rat cytoplasmic C1-tetrahydrofolate synthase gene and analysis of its expression in liver regeneration and fetal development. 1459 74

A retroprocessed pseudogene (retropseudogene) descended from the gene encoding ribonuclease (RNase) H1 has been found in ape genomes that preserves a splice junction mutation event that altered the carboxyl-terminal end of the enzyme. The GT --> GC transition mutant at the 5' splice junction of RNase H1 exon 7/intron 7 led to the absence of exon 8 and more than 1 kb of intron 7 sequence being substituted. Comparison of source gene and pseudogene sequences indicates that the retrotranscription event occurred 19 million years ago. Present in these sequences is an in-frame stop and several available polyadenylation signals, suggesting that the mutant allele could have been translated. At the present time, the genetic fossil is the only evidence that the mutation ever occurred, and thus represents an archival marker of an ancient genetic event in primate evolution.
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PMID:An ancient RNase H1 splice junction mutant preserved in a 19-million-year-old genetic fossil in ape genomes. 1522 Mar 93

Two approaches, one novel, are applied to analyze the divergent evolution of ruminant seminal ribonucleases (RNases), paralogs of the well-known pancreatic RNases of mammals. Here, the goal was to identify periods of divergence of seminal RNase under functional constraints, periods of divergence as a pseudogene, and periods of divergence driven by positive selection pressures. The classical approach involves the analysis of nonsynonymous to synonymous replacements ratios (omega) for the branches of the seminal RNase evolutionary tree. The novel approach coupled these analyses with the mapping of substitutions on the folded structure of the protein. These analyses suggest that seminal RNase diverged during much of its history after divergence from pancreatic RNase as a functioning protein, followed by homoplastic inactivations to create pseudogenes in multiple ruminant lineages. Further, they are consistent with adaptive evolution only in the most recent episode leading to the gene in modern oxen. These conclusions contrast sharply with the view, cited widely in the literature, that seminal RNase decayed after its formation by gene duplication into an inactive pseudogene, whose lesions were repaired in a reactivation event. Further, the 2 approaches, omega estimation and mapping of replacements on the protein structure, were compared by examining their utility for establishing the functional status of the seminal RNase genes in 2 deer species. Hog and roe deer share common lesions, which strongly suggests that the gene was inactive in their last common ancestor. In this specific example, the crystallographic approach made the correct implication more strongly than the omega approach. Studies of this type should contribute to an integrated framework of tools to assign functional and nonfunctional episodes to recently created gene duplicates and to understand more broadly how gene duplication leads to the emergence of proteins with novel functions.
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PMID:The evolution of seminal ribonuclease: pseudogene reactivation or multiple gene inactivation events? 1726 22

Gametophytic self-incompatibility (GSI) of Rosaceae, Solanaceae and Plantaginaceae is controlled by a complex S locus that encodes separate proteins for pistil and pollen specificities, extracellular ribonucleases (S-RNases) and F-box proteins SFB/SLF, respectively. SFB/SLFs of Prunus (subfamily Prunoideae of Rosaceae), Solanaceae and Plantaginaceae are single copy in each S haplotype, while recently identified pollen S candidates SFBBs of subfamily Maloideae of Rosaceae, apple and Japanese pear, are multiple; two and three related SFBBs were isolated from each S haplotype of apple and Japanese pear, respectively. Here, we show that apple (Malus x domestica) SFBBs constitute a gene family that is much larger than initially thought. Twenty additional SFBB-like genes/alleles were isolated by screening of a BAC library derived from S (3) S (9) genotype, and tentatively named MdFBX1-20. All but one MdFBX showed S haplotype-specific polymorphisms. All the polymorphic MdFBXs were completely linked to S-RNase in 239 segregants. In addition, FISH revealed that the monomorphic gene MdFBX11 is also located near S-RNase, and the S locus is located in a subtelomeric region of a chromosome and is not close to the centromere. All MdFBXs were specifically expressed in pollen, except for a pseudogene MdFBX4 that showed no expression in any organs analyzed. Phylogenetic analysis revealed that the closest relatives of most MdFBXs were from a different S haplotype, suggesting that proliferation of MdSFBB/FBXs predates diversification of the S haplotypes.
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PMID:Apple S locus region represents a large cluster of related, polymorphic and pollen-specific F-box genes. 2062 88

Pancreatic ribonuclease (RNASE1) is a digestive enzyme that has been one of the key models in studies of evolutionary innovation and functional diversification. It has been believed that the RNASE1 gene duplications are correlated with the plant-feeding adaptation of foregut-fermenting herbivores. Here, we characterized RNASE1 genes from Caniformia, which has a simple digestive system and lacks microbial digestion typical of herbivores, in an unprecedented scope based on both gene sequence and tissue expression analyses. Remarkably, the results yielded new hypotheses regarding the evolution and the function of Caniformia RNASE1 genes. Four independent gene duplication events in the families of superfamily Musteloidea, including Procyonidae, Ailuridae, Mephitidae and Mustelidae, were recovered, rejecting previous Mustelidae-specific duplication hypothesis, but supporting Musteloidea duplication hypothesis. Moreover, our analyses revealed pronounced differences among the RNASE1 gene copies regarding their selection pressures, pI values and tissue expression patterns, suggesting the differences in their physiological functions. Notably, the expression analyses detected the transcription of a RNASE1 pseudogene in several tissues, raising the possibility that pseudogenes are also a potential source during the RNase functional diversification. In sum, the present work demonstrated a far more complex and intriguing evolutionary pattern and functional diversity of mammalian ribonuclease than previously thought.
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PMID:Evolutionary and functional novelty of pancreatic ribonuclease: a study of Musteloidea (order Carnivora). 2486 Nov 5


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