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)

The secondary structure of the portion of the transferrin receptor mRNA responsible for the regulation of the transcript's half-life has been deduced by ribonuclease H cleavage directed by antisense oligodeoxyribonucleotides as well as with other ribonucleases sensitive to RNA secondary structure. The data indicate that both a synthetic 252-nucleotide RNA and the comparable portion of a 2.7-kb cellular mRNA contain three stem-loops referred to as iron-responsive elements (IREs). This secondary structure appears to be relatively static, with little interconversion with another possible structure having a similar calculated free energy but involving longer-range base pairing. Deletion of a selected cytosine residue from each of the IRE loops has been shown to yield an unregulated, unstable mRNA. This altered RNA has a secondary structure similar, if not identical, to that of the RNA that is competent in regulation.
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PMID:The secondary structure of the regulatory region of the transferrin receptor mRNA deduced by enzymatic cleavage. 132 Mar 97

The Azotobacter vinelandii NafY protein (nitrogenase accessory factor Y) is able to bind either to the iron molybdenum cofactor (FeMo-co) or to apodinitrogenase and is believed to facilitate the transfer of FeMo-co into apodinitrogenase. The NafY protein has two domains: an N-terminal domain (residues Met1-Leu98) and a C-terminal domain (residues Glu99-Ser232), referred here to as the "core domain." The core domain of NafY is shown here to be capable of binding the FeMo cofactor of nitrogenase but unable to bind to apodinitrogenase in the absence of the first domain. The three-dimensional molecular structure of the core domain of NafY has been solved to 1.8-A resolution, revealing that the protein consists of a mixed five-stranded beta-sheet flanked by five alpha-helices that belongs to the ribonuclease H superfamily. As such, this represents a new fold capable of binding FeMo-co, where the only previous example was that seen in dinitrogenase.
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PMID:The three-dimensional structure of the core domain of Naf Y from Azotobacter vinelandii determined at 1.8-A resolution. 1275 95

Hereditary hemochromatosis (HH) is a condition in which intestinal iron absorption is greatly elevated. Present treatment is weekly phlebotomy, affecting quality of life and leading to recurrent infections. The iron transporter divalent metal transporter-1 (DMT-1) of enterocytes is responsible for iron uptake from the intestinal lumen; iron is further extruded into the blood by the basolateral transporter ferroportin-1. A therapeutic approach for HH could start with a long-term reduction of iron transport by reduction of DMT-1 levels. We designed an AAV vector coding for a short antisense RNA (AAV-DMT-1-AS) against DMT-1, which reduced iron uptake by 50-60% in human intestinal cells (Caco-2). At low infection levels, DMT-1 mRNA virtually disappeared, suggesting RNAi-like and/or RNase H antisense effects. DMT-1 mRNA levels returned to normal at higher infection levels, indicating that an additional mechanism of mRNA occupation, able to block DMT-1 translation and to avoid feedback regulation by iron responsive elements (IRE), also exists. Cell morphology was normal in all cases and no increases in the interferon-related responses, measured by (a) 2'-5' A oligo synthetase (b) IFITM1 and (c) ISGF3gamma mRNA levels, were observed. Studies presented herein indicate that enterocyte targeting with a gene coding for a short antisense against iron transport blocks enterocyte iron uptake, which may have therapeutic value.
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PMID:Antisense gene delivered by an adenoassociated viral vector inhibits iron uptake in human intestinal cells: potential application in hemochromatosis. 1589 35