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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria, organelles specialized in energy conservation reactions in eukaryotic cells, have evolved from eubacteria-like endosymbionts whose closest known relatives are the rickettsial group of alpha-proteobacteria. Because characterized mitochondrial genomes vary markedly in structure, it has been impossible to infer from them the initial form of the proto-mitochondrial genome. This would require the identification of minimally derived mitochondrial DNAs that better reflect the ancestral state. Here we describe such a primitive mitochondrial genome, in the freshwater protozoon Reclinomonas americana. This protist displays ultrastructural characteristics that ally it with the retortamonads, a protozoan group that lacks mitochondria. R. americana mtDNA (69,034 base pairs) contains the largest collection of genes (97) so far identified in any mtDNA, including genes for 5S ribosomal RNA, the RNA component of RNase P, and at least 18 proteins not previously known to be encoded in mitochondria. Most surprising are four genes specifying a multisubunit, eubacterial-type RNA polymerase. Features of gene content together with eubacterial characteristics of genome organization and expression not found before in mitochondrial genomes indicate that R. americana mtDNA more closely resembles the ancestral proto-mitochondrial genome than any other mtDNA investigated to date.
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PMID:An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. 916 3

4-Thiouridine, a photoreactive analogue of uridine, was randomly incorporated into yeast tRNA(Phe) precursor molecules by transcription with T7 RNA polymerase and the resulting transcripts were converted into mature tRNA(Phe) by treatment with RNase P RNA. The photoreactive tRNA(Phe) was aminoacylated and bound to the P site of Escherichia coli 70S ribosomes in the presence of a poly(U) template. Irradiation of the complexes with light of 300 nm resulted in the covalent crosslinking of nt U20 in the D loop of the tRNA to protein S11 of the 30S ribosomal subunit, whereas nt U33 in the anticodon loop crosslinked to 30S-subunit protein S7. These results allowed us to map the D loop of P site-bound tRNA to the platform of the 30S ribosomal subunit and provided additional information about contacts between protein S7 and the anticodon loop in the cleft between the platform and the subunit head.
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PMID:Photoaffinity labeling of 30S-subunit proteins S7 and S11 by 4-thiouridine-substituted tRNA(Phe) situated at the P site of Escherichia coli ribosomes. 929 1

Eukaryotic precursor (pre)-tRNAs are processed at both ends prior to maturation. Pre-tRNAs and other nascent transcripts synthesized by RNA polymerase III are bound at their 3' ends at the sequence motif UUUOH [3' oligo(U)] by the La antigen, a conserved phosphoprotein whose role in RNA processing has been associated previously with 3'-end maturation only. We show that in addition to its role in tRNA 3'-end maturation, human La protein can also modulate 5' processing of pre-tRNAs. Both the La antigen's N-terminal RNA-binding domain and its C-terminal basic region are required for attenuation of pre-tRNA 5' processing. RNA binding and nuclease protection assays with a variety of pre-tRNA substrates and mutant La proteins indicate that 5' protection is a highly selective activity of La. This activity is dependent on 3' oligo(U) in the pre-tRNA for interaction with the N-terminal RNA binding domain of La and interaction of the C-terminal basic region of La with the 5' triphosphate end of nascent pre-tRNA. Phosphorylation of La is known to occur on serine 366, adjacent to the C-terminal basic region. We show that this modification interferes with the La antigen's ability to protect pre-tRNAiMet from 5' processing either by HeLa extract or purified RNase P but that it does not affect interaction with the 3' end of pre-tRNA. These findings provide the first evidence to indicate that tRNA 5'-end maturation may be regulated in eukaryotes. Implications of triphosphate recognition is discussed as is a role for La phosphoprotein in controlling transcriptional and posttranscriptional events in the biogenesis of polymerase III transcripts.
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PMID:5' processing of tRNA precursors can Be modulated by the human La antigen phosphoprotein. 958 61

We compared in vitro transcription-initiated folding of the ribozyme from Bacillus subtilis RNase P to refolding from the full-length, denatured state by monitoring the appearance of its catalytic activity. At 37 degrees C, Mg(2+)-initiated refolding of the wild type and a circularly permutate ribozyme takes minutes and is limited by a kinetic trap. Transcription by T7 RNA polymerase alters the folding pathway of both RNAs and introduces new kinetic traps. Transcription by the core Escherichia coli RNA polymerase yields the same result, in spite of its 4-fold-slower elongation rate. However, the presence of its elongation factor NusA accelerates more than 10-fold the transcription-initiated folding of the circularly, permutated ribozyme by E. coli RNA polymerase. The effect of NusA likely is caused by its enhancement of transcriptional pausing because NusA did not accelerate transcription-initiated folding using a mutant RNA polymerase that failed to pause or respond to NusA during ribozyme synthesis. We conclude that both transcription and specific pausing therein can alter RNA-folding pathways.
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PMID:Folding of a large ribozyme during transcription and the effect of the elongation factor NusA. 1044 29

Poly(ADP-ribose) polymerase 2 (PARP-2) is a DNA damage-dependent enzyme that belongs to a growing family of enzymes seemingly involved in genome protection. To gain insight into the physiological role of PARP-2 and to investigate mechanisms of PARP-2 gene regulation, we cloned and characterized the murine PARP-2 gene. The PARP-2 gene consists of 16 exons and 15 introns spanning about 13 kilobase pairs. Interestingly, the PARP-2 gene lies head to head with the gene encoding the mouse RNase P RNA subunit. The distance between the transcription start sites of the PARP-2 and RNase P RNA genes is 114 base pairs. This suggested that regulation of the expression of both genes may be coordinated through a bi-directional promoter. The PARP-2/RNase P RNA gene organization is conserved in the human. To our knowledge, this is the first report of a RNA polymerase II gene and an RNA polymerase III gene sharing the same promoter region and potentially the same transcriptional control elements. Reporter gene constructs showed that the 113-base pair intergenic region was indeed sufficient for the expression of both genes and revealed the importance of both the TATA and the DSE/Oct-1 expression control elements for the PARP-2 gene transcription. The expression of both genes is clearly independently regulated. PARP-2 is expressed only in certain tissues, and RNase P RNA is expressed in all tissues. This suggests that both genes may be subjected to multiple levels of control and may be regulated by different factors in different cellular contexts.
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PMID:A bidirectional promoter connects the poly(ADP-ribose) polymerase 2 (PARP-2) gene to the gene for RNase P RNA. structure and expression of the mouse PARP-2 gene. 1113 88

H1 RNA, the RNA component of the human nuclear RNase P, is encoded by a unique gene transcribed by RNA polymerase III (Pol III). In this work, cis-acting elements and trans-acting factors involved in human H1 gene transcription were characterized by transcription assays of mutant templates and DNA binding assays of recombinant proteins. Four elements, lying within 100 bp of 5'-flanking sequences, were defined to be essential for maximal in vitro and in vivo expression, consisting of the octamer, Staf, proximal sequence element (PSE) and TATA motifs. These are also encountered in the promoter elements of vertebrate snRNA genes, where the first two constitute the distal sequence element (DSE). In all the genes examined so far, the DSE is distant from the PSE and TATA box that compose the basal promoter. However, we observed a fundamental difference in the organization of the H1 RNA and snRNA gene promoters with respect to the relative spacing of the DSE and PSE. Indeed, the H1 promoter is unusually compact, with the octamer motif and Staf binding site adjacent to the PSE and TATA motifs. It thus appears that the human RNase P RNA gene has adopted a unique promoter strategy placing the DSE immediately adjacent to the basal promoter.
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PMID:An unusually compact external promoter for RNA polymerase III transcription of the human H1RNA gene. 1141 Jun 57

After transcription by RNA polymerase (pol) III, nascent Pol III transcripts pass through RNA processing, modification, and transport machineries as part of their posttranscriptional maturation process. The first factor to interact with Pol III transcripts is La protein, which binds principally via its conserved N-terminal domain (NTD), to the UUU-OH motif that results from transcription termination. This review includes a sequence Logo of the most conserved region of La and its refined modeling as an RNA recognition motif (RRM). La protects RNAs from 3' exonucleolytic digestion and also contributes to their nuclear retention. The variety of modifications found on La-associated RNAs is reviewed in detail and considered in the contexts of how La may bind the termini of structured RNAs without interfering with recognition by modification enzymes, and its ability to chaperone RNAs through multiple parts of their maturation pathways. The CTD of human La recognizes the 5' end region of nascent RNA in a manner that is sensitive to serine 366 phosphorylation. Although the CTD can control pre-tRNA cleavage by RNase P, a rate-limiting step in tRNASerUGA maturation, the extent to which it acts in the maturation pathway(s) of other transcripts is unknown but considered here. Evidence that a fraction of La resides in the nucleolus together with recent findings that several Pol III transcripts pass through the nucleolus is also reviewed. An imminent goal is to understand how the bipartite RNA binding, intracellular trafficking, and signal transduction activities of La are integrated with the maturation pathways of the various RNAs with which it associates.
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PMID:La protein and its associated small nuclear and nucleolar precursor RNAs. 1186 87

The essential Saccharomyces cerevisiae gene BDP1 encodes a subunit of RNA polymerase III (Pol III) transcription factor (TFIIIB); TATA box binding protein (TBP) and Brf1 are the other subunits of this three-protein complex. Deletion analysis defined three segments of Bdp1 that are essential for viability. A central segment, comprising amino acids 327 to 353, was found to be dispensable, and cells making Bdp1 that was split within this segment, at amino acid 352, are viable. Suppression of bdp1 conditional viability by overexpressing SPT15 and BRF1 identified functional interactions of specific Bdp1 segments with TBP and Brf1, respectively. A Bdp1 deletion near essential segment I was synthetically lethal with overexpression of PCF1-1, a dominant gain-of-function mutation in the second tetracopeptide repeat motif (out of 11) of the Tfc4 (tau(131)) subunit of TFIIIC. The analysis also identifies a connection between Bdp1 and posttranscriptional processing of Pol III transcripts. Yeast genomic library screening identified RPR1 as the specific overexpression suppressor of very slow growth at 37 degrees C due to deletion of Bdp1 amino acids 253 to 269. RPR1 RNA, a Pol III transcript, is the RNA subunit of RNase P, which trims pre-tRNA transcript 5' ends. Maturation of tRNA was found to be aberrant in bdp1-Delta 253-269 cells, and RPR1 transcription with the highly resolved Pol III transcription system in vitro was also diminished when recombinant Bdp1 Delta 253-269 replaced wild-type Bdp1. Physical interaction of RNase P with Bdp1 was demonstrated by coimmunoprecipitation and pull-down assays.
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PMID:Essential roles of Bdp1, a subunit of RNA polymerase III initiation factor TFIIIB, in transcription and tRNA processing. 1197 60

Depletion of any of the five essential proteins Lsm2p to Lsm5p and Lsm8p leads to strong accumulation of all tested unspliced pre-tRNA species, as well as accumulation of 5' and 3' unprocessed species. Aberrant 3'-extended pre-tRNAs were detected, presumably due to stabilization of transcripts that fail to undergo correct transcription termination, and the accumulation of truncated tRNA fragments was also observed. Tandem affinity purification-tagged Lsm3p was associated with pre-tRNA primary transcripts and, less efficiently, with other unspliced pre-tRNA intermediates but not mature tRNAs. Association of the Saccharomyces cerevisiae La homologue Lhp1p with pre-tRNAs was reduced approximately threefold on depletion of Lsm3p or Lsm5p. The association of Lhp1p with larger RNA polymerase III transcripts, pre-RNase P RNA and the signal recognition particle RNA (scR1), was more drastically reduced. The impaired pre-tRNA processing seen on Lsm depletion is not, however, due solely to reduced Lhp1p association as evidenced by analysis of lhp1-Delta strains depleted of Lsm3p or Lsm5p. These data are consistent with roles for an Lsm complex as a chaperone that facilitates the efficient association of pre-tRNA processing factors with their substrates.
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PMID:Lsm proteins are required for normal processing of pre-tRNAs and their efficient association with La-homologous protein Lhp1p. 1207 51

The causative agent of Whipple's disease, Tropheryma whipplei, is a slow-growing bacterium that remains poorly-understood. Genetic characterization of this organism has relied heavily upon rRNA sequence analysis. Pending completion of a complete genome sequencing effort, we have characterized several conserved non-rRNA genes from T. whipplei directly from infected tissue using broad-range PCR and a genome-walking strategy. Our goals were to evaluate its phylogenetic relationships, and to find ways to expand the strain typing scheme, based on rDNA sequence comparisons. The genes coding for the ATP synthase beta subunit (atpD), elongation factor Tu (tuf), heat shock protein GroEL (groEL), beta subunit of DNA-dependent RNA polymerase (rpoB), and RNase P RNA (rnpB) were analyzed, as well as the regions upstream and downstream of the rRNA operon. Phylogenetic analyses with all non-rRNA marker molecules consistently placed T. whipplei within the class, Actinobacteria. The arrangement of genes in the atpD and rpoB chromosomal regions was also consistent with other actinomycete genomes. Tandem sequence repeats were found upstream and downstream of the rRNA operon, and downstream of the groEL gene. These chromosomal sites and the 16S-23S rRNA intergenic spacer regions were examined in the specimens of 11 patients, and a unique combination of tandem repeat numbers and spacer polymorphisms was found in each patient. These data provide the basis for a more discriminatory typing method for T. whipplei.
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PMID:Analysis of conserved non-rRNA genes of Tropheryma whipplei. 1274 4


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