Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.4 (RNase H)
 2,751 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conjugates of mitomycin C (MC) and 15-mer oligodeoxyribonucleotides (ODNs) were synthesized in which the 7-amino group of MC was tethered by either a (-CH2-)6 or a (-CH2-)12 linker to the 5'-terminal phosphate of the ODNs. The conjugates were shown to be cross-linked selectively to complementary 18-mer oligoribonucleotides (ORNs). The cross-linking was dependent on reductive activation of the MC moiety of the conjugates by NADPH-cytochrome c reductase/NADPH. The cross-linked ODN-ORN hybrid duplexes were characterized as such by degeneration by RNase H. Cross-linking efficiencies of the conjugates were 50 and 25% in the case of the (-CH2-)12 tether and the (-CH2-)6 tether respectively The results demonstrate the feasibility of sequence-targeted alkylation of RNA by MC via antisense recognition.
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PMID:Antisense sequence-directed cross-linking of RNA oligonucleotides by mitomycin. 931 56

Thyroid hormone [triiodothyronine (T3)] positively regulates NADPH cytochrome P450 reductase (P450R) mRNA expression in rat liver, with P450R transcription initiation being a key regulated step. T3 is presently shown to have significant post-transcriptional effects on P450R expression. T3 increased the size of cytoplasmic P450R mRNA by approximately 105 nucleotides 12 h after T3 treatment, followed by a return to basal levels at 24 h. Primer extension analysis and Northern hybridization with 5'-untranslated region probes revealed no change in P450R mRNA 5' structure with T3 treatment. By contrast, RNase H analysis revealed a transient, T3-induced increase in P450R mRNA poly(A) tail, from approximately 100 to approximately 205 A. This increase in P450R polyadenylation, detectable in the nucleus 8 h after T3 treatment and in the cytoplasm at 12 h, was transient and was reversed by 16 h, when the T3-induced accumulation of cytoplasmic P450R mRNA was near maximal. Actinomycin D blocked the increase in P450R poly(A) tail and the induction of P450R mRNA, indicating a requirement for ongoing gene transcription for both T3 responses. T3 treatment destabilized P450R mRNA in rat liver in vivo, as shown by the T3-dependent 6-fold decrease in cytoplasmic P450R mRNA half-life, from a basal value of >or=16 h in uninduced liver to approximately 2.5 h, measured 24 h after T3 administration. These findings demonstrate that T3 increases nuclear polyadenylation of P450R RNA as a transient, early regulatory response and that this response is temporally dissociated from the subsequent decrease in cytoplasmic P450R mRNA stability.
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PMID:Post-transcriptional regulation of hepatic NADPH-cytochrome P450 reductase by thyroid hormone: independent effects on poly(A) tail length and mRNA stability. 1196 Nov 26