Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine synthetase (GS) converts ammonia and glutamate into glutamine. We assessed the activity of the 5' regulatory region of the GS gene in developing transgenic mice carrying the chloramphenicol acetyltransferase (CAT) gene under the control of 3150 bp of the upstream sequence of the rat GS gene to obtain insight into the spatiotemporal regulation of its pattern of expression. To determine the organ-specific activity of the 5' regulatory region CAT and GS mRNA expression were compared by ribonuclease-protection and semi-quantitative in situ hybridization analyses. Three patterns were observed: the 5' region is active and involved in the regulation of GS expression throughout development (pericentral hepatocytes, intestines and epididymis); the 5' region shows no activity at any of the ages investigated (periportal hepatocytes and white adipose tissue); and the activity of the 5' region becomes repressed during development (stomach, muscle, brown adipose tissue, kidney, lung and testis). In the second group, an additional element must be responsible for the activation of GS expression. The last group included organs in which the 5' regulatory region is active, but not in the cells that express GS. In these organs, the activity of the 5' regulatory region must be repressed by other regulatory regions of the GS gene that are missing from the transgenic construct. These findings indicate that in addition to the 5' regulatory region, at least two unidentified elements are involved in the spatiotemporal pattern of expression of GS.
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PMID:Organ-specific activity of the 5' regulatory region of the glutamine synthetase gene in developing mice. 934 14

We report on the combination of chemical mutagenesis, azithromycin selection and next-generation sequencing (Mut-Seq) for the identification of small nucleotide variants that decrease the susceptibility of Streptococcus pneumoniae to the macrolide antibiotic azithromycin. Mutations in the 23S ribosomal RNA or in ribosomal proteins can confer resistance to macrolides and these were detected by Mut-Seq. By concentrating on recurrent variants, we could associate mutations in genes implicated in the metabolism of glutamine with decreased azithromycin susceptibility among S. pneumoniae mutants. Glutamine synthetase catalyses the transformation of glutamate and ammonium into glutamine and its chemical inhibition is shown to sensitize S. pneumoniae to antibiotics. A mutation affecting the ribosomal-binding site of a putative ribonuclease J2 is also shown to confer low-level resistance. Mut-Seq has the potential to reveal chromosomal changes enabling high resistance as well as novel events conferring more subtle phenotypes.
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PMID:Azithromycin resistance mutations in Streptococcus pneumoniae as revealed by a chemogenomic screen. 3307 87