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)

Transcription termination factor Rho from Micrococcus luteus, a high G + C Gram-positive bacterium, contains an unusual extra sequence within its RNA binding domain that is rich in Arg, Glu, and Asp residues and deficient in hydrophobic residues. To determine the role of this extra sequence, we compared the biochemical properties of a variant lacking nearly all the extra sequence, des(60-300) Rho, to that of wild-type M. luteus Rho. The two forms had very similar properties except that the des(60-300) Rho was unable to terminate transcription with Escherichia coli RNA polymerase at the promoter proximal sites used by the wild-type Rho on a lambda cro DNA template but could cause termination at more distal sites and did cause termination at proximal sites when ITP replaced GTP in the reaction mixture. The RNA binding properties of the two forms of this Rho with normal and inosine-substituted RNAs were found to correlate fully with their termination properties. These results indicate that the arginine-rich extra sequence is directly involved in the selection of the termination site and support the hypothesis that the sequence is present in M. luteus Rho to facilitate its binding to M. luteus transcripts, which are likely to have a high degree of base-paired secondary structure because of their high proportion of G residues.
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PMID:Function of the novel subdomain in the RNA binding domain of transcription termination factor Rho from Micrococcus luteus. 899 24

Acetylcholinesterase (AChE) is expressed in murine megakaryocytes (MK), where its antisense inhibition suppresses differentiation, yet was never detected in human MK. Here, we report that AChE is produced in normal human bone marrow MK and in cell lines derived thereof. Reverse transcriptase-polymerase chain reaction (RT-PCR) amplification showed two ACHEmRNA forms in human megakaryoblastic DAMI cells. In situ hybridization demonstrated ACHEmRNA surrounding the nucleus of small DAMI cells and the nuclear lobes of large, polyploid cells. Differentiation induction with phorbol ester and exposure to recombinant human thrombopoietin suppressed both ACHEmRNA and AChE activity. The residual AChE in mature differentiated cells acquired higher stability and detergent-sensitivity as compared with AChE in small proliferating cells. AChE activity was primarily associated with nuclei of both DAMI cells and small (10 microm) primary proliferating human bone marrow MK identified with GPIIb/IIIa antibodies. This activity was significantly reduced in medium size MK (10 to 25 microm) and was almost undetectable in large MK (>25 microm), yet was twofold more abundant in some large MK from idiopathic thrombocytopenia purpura (ITP) patients with accelerated MK maturation. The loss of AChE activity at the transition from proliferating to differentiating MK highlights species-specific differences in its expression, suggesting a distinct role for AChE in human MK development.
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PMID:Immature human megakaryocytes produce nuclear-associated acetylcholinesterase. 916 Jun 69

An RNA that replicates with core RNA polymerase from E. coli and the substrates ATP, CTP, ITP, and UTP, was selected from a random poly(A,U,I,C) library and named EcorpI. Another replicating RNA, EcorpG, was obtained by template-free incubation of holo RNA polymerase and the substrates ATP, CTP, GTP, and UTP. Both RNA species showed typical autocatalytic RNA amplification profiles with replication rates in the range of other RNA replicons. The replication products were heterogeneous in length; the different lengths appeared to be different replication intermediates. Both RNA were single-stranded with much internal base-pairing but low melting points. Their sequences were composed by permutations of certain sequence motives in both polarities separated by short oligo(A) and oligo(U) clusters. There was evidence for 3'-terminal elongation on an intramolecular template. No double-stranded RNA was found, even though base-pairing is certainly the underlying basis of the replication process. The reaction was highly sensitive: a few RNA strands were sufficient to trigger an amplification avalanche.
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PMID:RNA species that replicate with DNA-dependent RNA polymerase from Escherichia coli. 1125 50

The contribution of P2 receptors to vasoconstriction of mouse mesenteric arteries was determined using wild-type (WT) and P2X(1) receptor-deficient (KO) animals. alpha,beta-methylene ATP (alpha,beta-meATP) and ATP evoked transient inward currents and constrictions of WT mesenteric arteries. In contrast, alpha,beta-meATP (100 microM) and ATP (100 microM) failed to evoke responses in KO arteries from a range of vascular beds. Nerve stimulation (100 pulses at 10 Hz) evoked constrictions of mesenteric arteries. For WT arteries, the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'-5'-disulfonate (PPADS) (30 microM) reduced the amplitude of response by approximately 50%; the residual constriction was abolished by prazosin (0.1 microM). In KO mice, vasoconstriction induced by nerve stimulation was reduced in amplitude by approximately 50%, unaffected by PPADS, but was abolished by prazosin. ADP (1 mM) (a P2Y(1), P2Y(12), and P2Y(13) receptor agonist) was ineffective. Because ATP had no effect on mesenteric artery tone from KO mice, this rules out the contribution of P2Y(2) receptors. The P2Y(4) receptor agonist ITP also failed to contract mesenteric arteries. However, UTP and UDP evoked sustained contractions of mesenteric arteries with similar potency (EC(50) approximately 10 microM). Complementary studies using reverse-transcriptase polymerase chain reaction showed that mesenteric arteries express P2Y(1), P2Y(2), and P2Y(6) receptors. These results demonstrate that homomeric P2X(1) receptors underlie the artery smooth muscle P2X receptor phenotype and contribute approximately 50% to sympathetic neurogenic vasoconstriction and indicate the presence of a UTP- and UDP-sensitive P2Y(6)-like receptor, but not vasoconstrictor P2Y(2) or P2Y(4) receptors, on mouse mesenteric arteries.
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PMID:P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries. 1243 12

Derangement of cellular immunity is central in the pathophysiology of adult autoimmune/idiopathic thrombocytopenic purpura (ITP). Herein we investigated cytokine gene expression in peripheral blood mononuclear cells (PBMCs) of adult chronic ITP patients and attempted to correlate cytokine polarization with the degree of thrombocytopenia. We used semiquantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) to measure the expression of type-1 (interleukin-2 [IL-2], interferon gamma [IFN-gamma]) and type-2 (IL-4, IL-5, IL-10, IL-3, IL-13) cytokines by PBMCs from 21 patients and 11 controls. Plasma transforming growth factor beta1 (TGF-beta1) levels were measured by enzyme-linked immunoassay (ELISA). T helper 1 (Th1)/Th2 ([IL-2 + IFN-gamma]/[IL-4 + IL-5]) cytokine mRNA ratios, thought to reflect the Th deviation of the pathogenic disease-specific T cells, and type-1/type-2 mRNA ratios, thought to reflect the overall immune response polarization, were significantly increased in ITP patients. The Th1/Th2 ratio was inversely correlated with platelet counts. TGF-beta1 levels appeared suppressed in patients with active disease, though not significantly. Our findings show a clear type-1 cytokine polarization of the autoimmune response in adult ITP that persists irrespective of disease status.
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PMID:Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. 1467 Sep 26

Human cytomegalovirus (HCMV) late mRNA expression in megakaryoblast and in turn the pathogenesis of idiopathic thrombocytopenic purpura (ITP) patients with HCMV infection, and effectiveness of ganciclovir were investigated. Colony forming unit-megakaryocytes (CFU-MK) of 46 ITP patients with HCMV infection were incubated from patients' bone marrow mononuclear cells (MNC). Reverse transcriptase-polymerase chain reaction (RT-PCR) was subsequently used for CFU-MK for HCMV-late mRNA detection. Ganciclovir therapy was given to both HCMV-late mRNA positive and negative groups for comparison of therapeutic effectiveness. The results in 19 of 46 CFU-MK culture cells specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay (ELISA) in the correspondent serum of peripheral blood were positive for HCMV-late mRNA. Sixteen out of 19, patients with positive HCMV-late mRNA CFU-MK had a positive response to ganciclovir. Amongst 27 patients with negative HCMV-late mRNA CFU-MK, only 4 positive responders to ganciclovir therapy were observed. Curative effectiveness of ganciclovir in HCMV-late mRNA positive group was significantly higher than that in HCMV-late mRNA negative group (P<0.01). It was suggested that HCMV could directly infect CFU-MK, which might be one of the mechanisms responsible for HCMV related ITP. The ganciclovir is an effective therapy in resulting in the increases in thrombocyte in the ITP patients whose HCMV- late mRNA was positive in their CFU-MK.
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PMID:Direct infection of colony forming unit-megakaryocyte by human cytomegalovirus contributes the pathogenesis of idiopathic thrombocytopenic purpura. 1721 66


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