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)

Directed indels, insertions, and deletions within paralogous genes, have the potential to root the tree of life. Here we apply a newly developed rooting algorithm, top-down rooting, to indels found in informational and operational gene sets, introduce new computational tools for indel analyses, and present evidence (P < .01) that the root of the tree of life is not present in its traditional location, between the Eubacteria and the Archaebacteria. Using indels contained in the dihydroorotate dehydrogenase/uroporphyrinogen decarboxylase gene pair and in the ribosomal protein S12/beta prime subunit of the RNA polymerase gene pair, we exclude the root from within the clade consisting of the Firmicutes plus the Archaebacteria and their most recent common ancestor. These results, plus previous directed indel studies excluding the root from the eukaryotes, restrict the root to just four possible sites. One potential root is on the branch leading to the double-membrane prokaryotes, another is on the branch leading to the Actinobacteria, another is within the Actinobacteria, and the fourth is on the branch leading to the Firmicutes-Archaea clade. These results imply (1) that the cenancestral population was not hyperthermophilic, but moderate thermophily cannot be excluded for the root on the branch leading to the Firmicutes-Archaea clade, (2) that the cenancestral population was surrounded by ester lipids and a peptidoglycan layer, and (3) that parts of the mevalonate synthesis pathway were present in the population ancestral to the Bacilli and the Archaebacteria, including geranylgeranylglyceryl phosphate synthase, an enzyme thought to be partially responsible for the unique sn-1 stereochemistry of the archaeal glycerol phosphate backbone.
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PMID:Evidence for a gram-positive, eubacterial root of the tree of life. 1751 83

Heme is an essential prosthetic group of proteins involved in oxygen transport, energy metabolism and nitric oxide production. ALAS1 (5-aminolevulinate synthase) is the rate-limiting enzyme in heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). In primary human hepatocytes and in HepG2 cells, PPARalpha agonists induced an increase in ALAS1 mRNA levels, which was abolished by PPARalpha silencing. These effects are mediated by two functional PPAR binding sites at positions -9 and -2.3 kb relative to the ALAS1 transcription start site. PPARalpha ligand treatment also up-regulated the mRNA levels of the genes ALAD (5-aminolevulinate dehydratase), UROS (uroporphyrinogen III synthase), UROD (uroporphyrinogen decarboxylase), CPOX (coproporphyrinogen oxidase) and PPOX (protoporphyrinogen oxidase) encoding for enzymes controlling further steps in heme biosynthesis. In HepG2 cells treated with PPARalpha agonists and in mouse liver upon fasting, the association of PPARalpha, its partner retinoid X receptor, PPARgamma co-activator 1alpha and activated RNA polymerase II with the transcription start site region of all six genes was increased, leading to higher levels of the metabolite heme. In conclusion, these data strongly support a role of PPARalpha in the regulation of human ALAS1 and of five additional genes of the pathway, consequently leading to increased heme synthesis.
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PMID:Peroxisome proliferator-activated receptor alpha controls hepatic heme biosynthesis through ALAS1. 2107 84