Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNase MRP is a site-specific ribonucleoprotein endoribonuclease that cleaves RNA from the mitochondrial origin of replication in a manner consistent with a role in priming leading-strand DNA synthesis. Despite the fact that the only known RNA substrate for this enzyme is complementary to mitochondrial DNA, the majority of the RNase MRP activity in a cell is found in the nucleus. The recent characterization of this activity in Saccharomyces cerevisiae and subsequent cloning of the gene coding for the RNA subunit of the yeast enzyme have enabled a genetic approach to the identification of a nuclear role for this ribonuclease. Since the gene for the RNA component of RNase MRP, NME1, is essential in yeast cells and RNase MRP in mammalian cells appears to be localized to nucleoli within the nucleus, we utilized both regulated expression and temperature-conditional mutations of NME1 to assay for a possible effect on rRNA processing. Depletion of the RNA component of the enzyme was accomplished by using the glucose-repressed GAL1 promoter. Shortly after the shift to glucose, the RNA component of the enzyme was found to be depleted severely, and rRNA processing was found to be normal at all sites except the B1 processing site. The B1 site, at the 5' end of the mature 5.8S rRNA, is actually composed of two cleavage sites 7 nucleotides apart. This cleavage normally generates two species of 5.8S rRNA at a ratio of 10:1 (small to large) in most eukaryotes. After RNase MRP depletion, yeast cells were found to have almost exclusively the larger species of 5.8S rRNA. In addition, an aberrant 309-nucleotide precursor that stretched from the A2 to E processing sites of rRNA accumulated in these cells. Temperature-conditional mutations in the RNase MRP RNA gene gave an identical phenotype. Translation in yeast cells depleted of the smaller 5.8S rRNA was found to remain robust, suggesting a possible function for two 5.8S rRNAs in the regulated translation of select messages. These results are consistent with RNase MRP playing a role in a late step of rRNA processing. The data also indicate a requirement for having the smaller form of 5.8S rRNA, and they argue for processing at the B1 position being composed of two separate cleavage events catalyzed by two different activities.
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PMID:Nuclear RNase MRP is required for correct processing of pre-5.8S rRNA in Saccharomyces cerevisiae. 824 8

We have isolated clones which complement the temperature sensitivity and abnormal rRNA processing pattern of the rrp2-2 mutant of Saccharomyces cerevisiae we previously described. DNA sequencing and restriction analysis demonstrated that all clones contain the NME1 gene encoding the RNA of the ribonucleprotein particle RNase MRP. Deletion analysis showed that the NME1 gene is responsible for the complementation of the rrp2-2 phenotype. A single base change was identified in the nme1 gene in the rrp2 mutant, confirming that the RRP2 and NME1 genes are identical. Our experiments therefore indicate that RNase MRP, in addition to its previously reported role in formation of RNA primers for mitochondrial DNA replication [Clayton, D. A. (1991) Trends Biochem. Sci. 16, 107-111], is involved in rRNA processing.
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PMID:The RNA of RNase MRP is required for normal processing of ribosomal RNA. 829 May 78

Human cells can become multidrug resistant (MDR) by an increase in the activity of the MDR1 P-glycoprotein or by other, as yet unknown mechanisms, referred to as non-P-glycoprotein mediated MDR (non-Pgp MDR). S. P. C. Cole et al. [Science (Washington DC), 258: 1650-1654, 1992] recently reported that in two cell lines non-Pgp MDR was associated with the overexpression of a new putative membrane transporter gene, MRP. Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW-1573 (non-small cell lung cancer) and GLC4 (small cell lung cancer). In all of ten SW-1573 derived lines examined the MRP mRNA level was equal to that in the parental line, whereas MRP was 25-fold overexpressed in a resistant subline of GLC4. We conclude that overexpression of MRP cannot account for all forms of non-Pgp MDR.
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PMID:Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. 846 91

RNase MRP and RNase P ribonucleoproteins are structurally and functionally similar across a large evolutionary distance. To better characterize possible complex interrelationships between these two enzymes, we have employed the fission yeast Schizosaccharomyces pombe. Unlike Saccharomyces cerevisiae, S. pombe is believed to harbour only one genetic locus for the RNA component of RNase P and does not contain a known mitochondrially encoded RNase P RNA. We have identified the single nuclear gene for the RNA component of RNase MRP in S. pombe, mrp-1, by homology to vertebrate RNase MRP RNAs. The mrp-1 gene encodes an RNA of maximum mature length 400 nucleotides that shares a high degree of identity, in evolutionarily conserved regions, to both vertebrate RNase MRP RNAs and S. pombe RNase P RNA. Disruption of mrp-1 in the diploid strain SP826 and sporulation of tetrads resulted in a 2 dead:2 viable segregation, consistent with the gene being essential. Lethality is rescued by a plasmid-borne copy of mrp-1. Partially purified ribonucleoprotein RNase MRP activity correctly and efficiently processed all previously characterized heterologous mitochondrial RNA substrates. The compact mitochondrial genome of S. pombe contains sequence elements with > 50% identity to mammalian D-loop CSBI and CSBII elements. The identification of mrp-1 in S. pombe should facilitate not only comparisons between the related ribonucleoproteins RNase MRP and RNase P, but should also provide an opportunity for genetic elucidation of RNase MRP function in a situation reflective of the animal kingdom.
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PMID:Schizosaccharomyces pombe RNase MRP RNA is homologous to metazoan RNase MRP RNAs and may provide clues to interrelationships between RNase MRP and RNase P. 855 96

The dynamic intra-nuclear localization of MRP RNA, the RNA component of the ribonucleoprotein enzyme RNase MRP, was examined in living cells by the method of fluorescent RNA cytochemistry (Wang, J., L.-G. Cao, Y.-L. Wang, and T. Pederson. 1991. Proc. Natl. Acad. Sci. USA. 88:7391-7395). MRP RNA very rapidly accumulated in nucleoli after nuclear microinjection of normal rat kidney (NRK) epithelial cells. Localization was specifically in the dense fibrillar component of the nucleolus, as revealed by immunocytochemistry with a monoclonal antibody against fibrillarin, a known dense fibrillar component protein, as well as by digital optical sectioning microscopy and 3-D stereo reconstruction. When MRP RNA was injected into the cytoplasm it was not imported into the nucleus. Nuclear microinjection of mutant MRP RNAs revealed that nucleolar localization requires a sequence element (nucleotides 23-62) previously implicated as a binding site for a nucleolar protein, the To antigen. These results demonstrate the dynamic localization of MRP RNA in the nucleus and provide important insights into the nucleolar targeting of MRP RNA.
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PMID:Dynamic localization of RNase MRP RNA in the nucleolus observed by fluorescent RNA cytochemistry in living cells. 855 35

RNase MRP is a ribonucleoprotein endoribonuclease found predominantly in nucleoli, but which has been associated with mitochondria and mitochondrial RNA processing. In order to analyze the intracellular localization of specific RNA components of ribonucleoproteins of this type, a whole-mount method for in situ hybridization in Xenopus laevis oocytes was employed. Results with specific probes (for both mitochondrial and nonmitochondrial RNAs) indicate that this procedure is generally effective for the detection of a variety of nucleic acids that reside in different cellular compartments. Probes used to detect the endogenous RNA component of RNase MRP (MRP RNA) during X. laevis oogenesis revealed a continuous nuclear signal as well as a possible dual localization of MRP RNA in nucleoli and mitochondria at developmental stages temporally consistent with both ribosomal and mitochondrial biogenesis. Genomic DNA encoding MRP RNA was injected into the nuclei of stage VI oocytes and correctly transcribed. The in vivo-transcribed RNA was properly assembled with at least some of its cognate proteins as demonstrated by immunoprecipitation with specific autoantiserum. In addition, detectable levels of the RNA were exported to the cytoplasm. This whole-mount procedure has permitted us to identify MRP RNA in situ at different developmental time points as well as during transcription of the injected gene, and suggests differential localization of MRP RNA during oogenesis consistent with its proposed function in both mitochondria and nucleoli.
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PMID:Distribution of RNase MRP RNA during Xenopus laevis oogenesis. 857 50

We report a detailed evolutionary study of the RNase P- and RNase MRP- associated RNAs. The analyses were performed on all the available complete sequences of RNase MRP (vertebrates, yeast, plant), nuclear RNase P (vertebrates, yeast), and mitochondrial RNase P (yeast) RNAs. For the first time the phylogenetic distance between these sequences and the nucleotide substitution rates have been quantitatively measured.The analyses were performed by considering the optimal multiple alignments obtained mostly by maximizing similarity between primary sequences. RNase P RNA and MRP RNA display evolutionary dynamics following the molecular clock. Both have similar rates and evolve about one order of magnitude faster than the corresponding small rRNA sequences which have been, so far, the most common gene markers used for phylogeny. However, small rRNAs evolve too slowly to solve close phylogenetic relationships such as those between mammals. The quicker rate of RNase P and MRP RNA allowed us to assess phylogenetic relationships between mammals and other vertebrate species and yeast strains. The phylogenetic data obtained with yeasts perfectly agree with those obtained by functional assays, thus demonstrating the potential offered by this approach for laboratory experiments.
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PMID:The evolution of the RNase P- and RNase MRP-associated RNAs: phylogenetic analysis and nucleotide substitution rate. 866 Apr 29

RNase P is a ribonucleoprotein endoribonuclease responsible for the 5' maturation of precursor tRNAs in all organisms. While analyzing mutations in conserved positions of the yeast nuclear RNase P RNA subunit, significant accumulation of an aberrant RNA of approximately 193 nucleotides was observed. This abundant RNA was identified as a 3'extended form of the 5.8S rRNA. This strain also displays a slightly elevated level of other rRNA processing intermediates with 5-ends at processing site A2 in the internal transcribed spacer 1 (ITS1) region of the rRNA primary transcript. To test whether pre-rRNA in the region of ITS1/5.8S/ITS2 is a substrate for RNase P in vitro, nuclear RNase P was partially purified to remove contaminating nucleases. Cleavage assays were performed using an rRNA substrate transcribed in vitro which includes the 5.8S region and its surrounding processing sites in ITS1 and ITS2. Discrete cleavages of this rRNA substrate were coincident with the peak fractions of nuclear RNase P, but not with fractions corresponding to mitochondrial RNase P or ribonuclease MRP RNA. The cleavage activity is sensitive to treatment with micrococcal nuclease, also consistent with an activity attributable to RNase R The strong RNase P cleavage sites were mapped and their possible relationships to steps in the rRNA processing pathway are considered. These observations suggest an intimate relationship between the processes of tRNA and rRNA maturation in the eukaryotic nucleus.
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PMID:An RNase P RNA subunit mutation affects ribosomal RNA processing. 877 95

Cleavage of the yeast pre-rRNA at site A(2) in internal transcribed spacer 1 (ITS1) requires multiple snoRNP species, whereas cleavage at site A(3),located 72 nt 3' in ITS1, requires Rnase MRP. Analyses of mutations in the pre- rRNA have revealed an unexpected link between processing at A(2) and A(3). Small substitution mutations in the 3' flanking sequence at A(2) inhibit processing at site A(3), whereas a small deletion at A(3) has been shown to delay processing at site A(2). Moreover, the combination of mutations in cis at both A(2) and A(3) leads to the synthesis of pre-rRNA species with 5' ends within the mature 18S rRNA sequence, at sites between + 482 and + 496. The simultaneous interference with an snoRNP processing complex at site A(2) and an Rnase MPRP complex at site A(3) may activate a pre-rRNA breakdown pathway. The same aberantpre-rRNA species are observed in strains with mutations in the RNA component of Rnase MRP, consistent with interactions between the processing complexes. Furthermore, genetic depletion of the snoRNA, snR30, has been shown to affect the coupling between cleavage by Rnase MRP and subsequent exonuclease digestion.We conclude that an sno-RNP-dependent processing complex that is required for A(2) cleavage and that recognizes the 3' flanking sequence at A(2), interacts with the RNase MRP complex bound to the pre-rRNA around site A(3).
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PMID:Processing of the yeast pre-rRNA at sites A(2) and A(3) is linked. 884 97

RNase MRP is a ribonucleoprotein originally identified on the basis of its ability to cleave RNA endonucleolytically from origins of mitochondrial DNA replication, rendering it a likely candidate for a role in priming leading-strand synthesis of mtDNA. In addition, a nuclear role for RNase MRP has been identified in yeast (Saccharomyces cerevisiae) ribosomal RNA processing. Consistent with a duality of function, RNase MRP has been localized to both mitochondria and nucleoli by in situ techniques. The RNA component of this ribonucleoprotein has been characterized from several different species. We previously cloned the gene for Xenopus laevis MRP RNA and showed that RNase MRP RNA is differentially expressed during amphibian development; in addition, the microinjected X. laevis RNase MRP RNA gene is correctly and efficiently transcribed in vivo. This article presents an analysis of the intracellular movement of in vivo-transcribed RNase MRP RNA in microinjected mature X. laevis oocytes. Although X. laevis MRP RNA is assembled into a ribonucleoprotein form and transported in an expected manner, human and mouse MRP RNAs exhibit markedly different transport patterns even though they are highly conserved in primary sequence. Furthermore, the only currently assigned protein (Th autoantigen) binding site in MRP RNA can be deleted without loss of nuclear export capacity. These results indicate that subtle determinants must exist for nucleocytoplasmic partitioning of this RNP and that the conserved Th autoantigen binding region appears unnecessary for the transit of in vivo-transcribed MRP RNA to the cytoplasm of mature X. laevis oocytes.
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PMID:Subtle determinants of the nucleocytoplasmic partitioning of in vivo-transcribed RNase MRP RNA in Xenopus laevis oocytes. 888 39


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