Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the possible involvement of dopamine receptors in the pathogenesis of various neurological disorders, we have cloned and sequenced a dopamine D2A receptor gene from the mouse. A mouse genomic library was screened with probes derived from the published sequence of a rat D2A receptor cDNA. Using restriction endonuclease mapping, Southern blotting, and DNA sequencing, we have determined the cDNA sequence and genomic organization of the mouse D2A receptor gene. Unlike other guanine nucleotide-binding protein-coupled receptors, but similar to its rat and human counterparts, the mouse D2A receptor gene has seven introns and spans at least 30 kb of genomic DNA. The mouse D2A sequence shows 99% amino acid homology with the rat and 95% amino acid homology with the human sequence. As would be predicted, sequence differences are significantly more frequent outside of the hypothesized transmembrane spanning domain regions of the protein. Using the polymerase chain reaction with primers made from neighboring exons, we have identified two alternatively spliced D2A transcripts in the mouse. However, in contrast to the other species studied, the mouse expresses primarily the mRNA representing the larger, 444-amino-acid form of the receptor. Mouse pituitary expresses only the mRNA of the 444-amino-acid form of the D2A receptor. Hence, the mouse may offer the best model to study the in vivo physiology of the long form of the D2A receptor.
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PMID:The mouse dopamine D2A receptor gene: sequence homology with the rat and human genes and expression of alternative transcripts. 186 Nov 51

To examine the roles of a short form of p53 in the regulation of apoptosis in chicken lymphoblastoid tumor cell lines derived from Marek's disease (MD) and avian leukosis (AL), the expressions of the p53 proteins were analyzed in these cell lines in which apoptosis was chemically induced. In MSB1-O derived from MD, the expression of a 40 kDa protein of p53 was decreased and that of a 32 kDa protein, a short form of p53, was increased during apoptosis induced by actinomycin D. In 1104B1 derived from AL, the expressions of 42 and 32 kDa of p53 were increased during the apoptosis. The short form of p53 was undetectable in these cell lines when apoptosis was blocked by the pretreatment with endonuclease inhibitor, Zn2+, protease inhibitors, TPCK and TLCK, or caspase inhibitor, Z-VAD-FMK. In the transcriptional level, the expressions of bcl-2 and IAP were decreased in these cell lines during actinomycin D-induced apoptosis, but no change was detected in the expression level of p53. These results suggest that, in these chicken tumors, the short form of p53 could play a role in the initiation of apoptosis induced by the chemotherapeutic compound, and that the regulation of its expression may be important for the maintenance of transformation status.
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PMID:The presence of a short form of p53 in chicken lymphoblastoid cell lines during apoptosis. 1682 Jul 12

Functional transfer RNA (tRNA) molecules are a prerequisite for protein biosynthesis. Several processing steps are required to generate the mature functional tRNA from precursor molecules. Two of the early processing steps involve cleavage at the tRNA 5' end and the tRNA 3' end. While processing at the tRNA 5' end is performed by RNase P, cleavage at the 3' end is catalyzed by the endonuclease tRNase Z. In eukaryotes, tRNase Z enzymes are found in two versions: a short form of about 250 to 300 amino acids and a long form of about 700 to 900 amino acids. All eukaryotic genomes analyzed to date encode at least one long tRNase Z protein. Of those, Arabidopsis (Arabidopsis thaliana) is the only organism that encodes four tRNase Z proteins, two short forms and two long forms. We show here that the four proteins are distributed to different subcellular compartments in the plant cell: the nucleus, the cytoplasm, the mitochondrion, and the chloroplast. One tRNase Z is present only in the cytoplasm, one protein is found exclusively in mitochondria, while the third one has dual locations: nucleus and mitochondria. None of these three tRNase Z proteins is essential. The fourth tRNase Z protein is present in chloroplasts, and deletion of its gene results in an embryo-lethal phenotype. In vitro analysis with the recombinant proteins showed that all four tRNase Z enzymes have tRNA 3' processing activity. In addition, the mitochondrial tRNase Z proteins cleave tRNA-like elements that serve as processing signals in mitochondrial mRNA maturation.
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PMID:Arabidopsis encodes four tRNase Z enzymes. 1941 72

Although tRNase Z from various organisms was shown to process nuclear tRNA 3' ends in vitro, only a very limited number of studies have reported its in vivo biological functions. tRNase Z is present in a short form, tRNase Z(S), and a long form, tRNase Z(L). Unlike Saccharomyces cerevisiae, which contains one tRNase Z(L) gene (scTRZ1) and humans, which contain one tRNase Z(L) encoded by the prostate-cancer susceptibility gene ELAC2 and one tRNase Z(S), Schizosaccharomyces pombe contains two tRNase Z(L) genes, designated sptrz1(+) and sptrz2(+). We report that both sptrz1(+) and sptrz2(+) are essential for growth. Moreover, sptrz1(+) is required for cell viability in the absence of Sla1p, which is thought to be required for endonuclease-mediated maturation of pre-tRNA 3' ends in yeast. Both scTRZ1 and ELAC2 can complement a temperature-sensitive allele of sptrz1(+), sptrz1-1, but not the sptrz1 null mutant, indicating that despite exhibiting species specificity, tRNase Z(L)s are functionally conserved among S. cerevisiae, S. pombe and humans. Overexpression of sptrz1(+), scTRZ1 and ELAC2 can increase suppression of the UGA nonsense mutation ade6-704 through facilitating 3' end processing of the defective suppressor tRNA that mediates suppression. Our findings reveal that 3' end processing is a limiting step for defective tRNA maturation and demonstrate that overexpression of sptrz1(+), scTRZ1 and ELAC2 can promote defective tRNA 3' processing in vivo. Our results also support the notion that yeast tRNase Z(L) is absolutely required for 3' end processing of at least a few pre-tRNAs even in the absence of Sla1p.
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PMID:Functional conservation of tRNase ZL among Saccharomyces cerevisiae, Schizosaccharomyces pombe and humans. 1955 50

tRNase Z is the endonuclease that is involved in tRNA 3'-end maturation by removal of the 3'-trailer sequences from tRNA precursors. Most eukaryotes examined to date, including the budding yeast Saccharomyces cerevisiae and humans, have a single long form of tRNase Z (tRNase ZL). In contrast, the fission yeast Schizosaccharomyces pombe contains two candidate tRNase ZLs encoded by the essential genes sptrz1+ and sptrz2+. In the present study, we have expressed recombinant SpTrz1p and SpTrz2p in S. pombe. Both recombinant proteins possess precursor tRNA 3'-endonucleolytic activity in vitro. SpTrz1p localizes to the nucleus and has a simian virus 40 NLS (nuclear localization signal)-like NLS at its N-terminus, which contains four consecutive arginine and lysine residues between residues 208 and 211 that are critical for the NLS function. In contrast, SpTrz2p is a mitochondrial protein with an N-terminal MTS (mitochondrial-targeting signal). High-level overexpression of sptrz1+ has no detectable phenotypes. In contrast, strong overexpression of sptrz2+ is lethal in wild-type cells and results in morphological abnormalities, including swollen and round cells, demonstrating that the correct expression level of sptrz2+ is critical. The present study provides evidence for partitioning of tRNase Z function between two different proteins in S. pombe, although we cannot rule out specialized functions for each protein.
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PMID:The fission yeast Schizosaccharomyces pombe has two distinct tRNase Z(L)s encoded by two different genes and differentially targeted to the nucleus and mitochondria. 2120 91

RNase Z is an endonuclease responsible for the removal of 3' extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase Z(L)) encoded by ELAC2, and a short form (RNase Z(S); ELAC1). We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase Z(S) was found in the cytosol, whereas RNase Z(L) localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase Z(L). Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase Z(L) is the enzyme involved in both, nuclear and mitochondrial tRNA 3' end maturation.
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PMID:Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation. 2155 54

tRNase Z is an essential endonuclease responsible for tRNA 3'-end maturation. tRNase Z exists in a short form (tRNase Z(S)) and a long form (tRNase Z(L)). Prokaryotes have only tRNase Z(S), whereas eukaryotes can have both forms of tRNase Z. Most eukaryotes characterized thus far, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and humans, contain only one tRNase Z(L) gene encoding both nuclear and mitochondrial forms of tRNase Z(L). In contrast, Schizosaccharomyces pombe contains two essential tRNase Z(L) genes (trz1 and trz2) encoding two tRNase Z(L) proteins, which are targeted to the nucleus and mitochondria, respectively. Trz1 protein levels are notably higher than Trz2 protein levels. Here, using temperature-sensitive mutants of trz1 and trz2, we provide in vivo evidence that trz1 and trz2 are involved in nuclear and mitochondrial tRNA 3'-end processing, respectively. In addition, trz2 is also involved in generation of the 5'-ends of other mitochondrial RNAs, whose 5'-ends coincide with the 3'-end of tRNA. Thus, our results provide a rare example showing partitioning of the nuclear and mitochondrial tRNase Z(L) activities between two different proteins in S. pombe. The evolution of two tRNase Z(L) genes and their differential expression in fission yeast may avoid toxic off-target effects.
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PMID:Partitioning of the nuclear and mitochondrial tRNA 3'-end processing activities between two different proteins in Schizosaccharomyces pombe. 2392 1