Disease relevance of UMP

• The VP55 (catalytic) subunit of vaccinia virus heterodimeric poly(A) polymerase (PAP) contacts 31-40 nucleotide segments of RNA in a uridylate-dependent manner, and effects the rapid, processive addition of a 30 nt oligo(A) tail [1].
• Analysis of mutated variants of the simian virus 40 late polyadenylation signal showed that uridylate-rich sequences located in the region between 30 and 55 nucleotides downstream of the cleavage site were required for efficient cross-linking of C proteins [2].
• Expression and sequence analysis of a cDNA encoding the orotidine-5'-monophosphate decarboxylase domain from Ehrlich ascites uridylate synthase [3].
• A highly conserved RNA structure in the 3' non-translated region of the SARS virus was cleaved preferentially at one of the unpaired uridylate bases, demonstrating that both RNA structure and base-pairing can affect cleavage by Nsp15 [4].
• A similar plasmid containing poliovirus cDNA was engineered to produce transcripts similarly lacking the first two uridylate residues of the poliovirus RNA sequence [5].

High impact information on UMP

• Direct visualization of uridylate deletion in vitro suggests a mechanism for kinetoplastid RNA editing [6].
• In the mitochondria of trypanosomatid protozoa the precursors of messenger RNAs (pre-mRNAs) have their coding information remodeled by the site-specific insertion and deletion of uridylate (U) residues [7].
• In TA3 mammary carcinoma cells in suspension culture, D-glucosamine X HCl (GlcN) induced a diversion of uridylate from UTP into UDP-N-acetylhexosamines, reducing the intracellular pool of UTP and eliciting an increased rate of de novo uridylate synthesis [8].
• Interplay of two uridylate-specific RNA binding sites in the translocation of poly(A) polymerase from vaccinia virus [1].
• Uridylate-containing RNA sequences determine specificity for binding and polyadenylation by the catalytic subunit of vaccinia virus poly(A) polymerase [9].

Chemical compound and disease context of UMP

• A very basic protein (pI approximately 11.0) was identified as uridylate kinase, an enzyme indirectly associated with pyrimidine biosynthesis and thought be absent in some members of the bacterial class Mollicutes [10].
• In experimental animals, UDP precursors uridine and uridine-5'-monophosphate (UMP) (both 30 mg/kg, administered intravenously 5 min before coronary occlusion) decreased the myocardium ischemic alteration index (1.9 and 3.5 times, respectively) and the T-wave amplitude within 60 min after occlusion [11].
• Rabbit antibodies directed against homogeneous uridylate synthase multienzyme from mouse Ehrlich ascites carcinoma precipitate both the orotidine-5'-monophosphate decarboxylase (EC 4.1.1.23) and orotate phosphoribosyltransferase (EC 2.4.2.10) activities of mouse and human erythrocyte uridylate synthase [12].

Biological context of UMP

• In mitochondria of Kinetoplastida belonging to the suborder Trypanosomatina, the nucleotide sequence of transcripts is post-transcriptionally edited via insertion and deletion of uridylate residues [13].
• An integrated computational and laboratory approach for selective amplification of mRNAs containing the adenylate uridylate-rich element consensus sequence [14].
• This binding has been shown in vitro to control the stability of adenylate uridylate-rich element-containing mRNAs, including mRNAs encoding proto-oncogenes, cytokines, or other signaling molecules [15].
• RNA editing in kinetoplastids is the post-transcriptional insertion and deletion of uridylate residues in mitochondrial transcripts, directed by base pairing with guide RNAs [16].
• Here, we report an interaction between the heterogeneous nuclear ribonucleoprotein (hnRNP) C protein, an abundant nuclear pre-mRNA binding protein, and the U6 snRNAs that have the longest uridylate stretches [17].

Anatomical context of UMP

• Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats [18].
• The incorporation rates of labeled orotic acid into poly(A)-containing mRNA isolated from polysomes are represented as the specific radioactivity (SR) (dpm/mg RNA) and the relative specific radioactivity (RSR) (dpm/mg RNA/dpm/mumoles of acid soluble uridine-5'-monophosphate (UMP] [19].
• The data suggest that Kupffer cells do not contribute to GalN-induced liver injury as a result of uridylate trapping [20].
• Both phosphate and uridylate derivates were also observed as main metabolites in the heart, lung, spleen and small intestine [21].
• After a localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UM), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively [22].

Associations of UMP with other chemical compounds

• In contrast, we found that orotidylate was released into the medium during the conversion of orotate to uridylate by cell-free extract of Plasmodium falciparum [23].
• We used several RNAs, including some with nucleotide analogs, and mass spectrometry to determine that Nsp15 cleaves only 3' of the recognition uridylate, with some cleavage 3' of cytidylate [4].
• Using reversed-phase high-performance liquid chromatography; the product (uridine) was separated from the substrate (uridine-5'-monophosphate) in less than 4 min [24].
• Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat [25].
• Computational analysis predicted three potential hydrophobic transmembrane alpha-helices within the Ura2 multidomain protein of Saccharomyces cerevisiae, the C-terminal subdomain of which catalyses the second step of uridine-monophosphate biosynthesis by its L-aspartate carbamoyltransferase activity (EC 2.1.3.2) [26].

Gene context of UMP

• AUF1/heterogeneous nuclear ribonucleoprotein D (hnRNPD) binds to adenylate uridylate-rich elements contained in the 3' untranslated region of many short-lived mRNAs [15].
• Although RRM 3 (of either TIA-1 or TIAR) does not interact with the uridylate-rich sequences selected by the full-length proteins, it is a bona fide RNA binding domain capable of affinity-precipitating a population of cellular RNAs ranging in size from 0.5 to 5 kilobases [27].
• The ecto-5'-nucleotidase readily hydrolyzed 5'-AMP and 5'-UMP [28].
• Additional methods including analysis of oligonucleotides following chemical blocking of uridylate residues with CMCT and analysis of products of incomplete enzymatic digestion are also discussed [29].
• The few transcripts synthesized in the absence of La have fewer uridylate residues at their 3' ends than those made in its presence [30].

Analytical, diagnostic and therapeutic context of UMP

• Additionally, mitochondrial extracts of cells with reduced band IV activity were deficient in catalyzing U-deletion, specifically at its ligation step, but were not deficient in U-insertion [31].
• A series of experiments, using cell culture models or in vitro assays, has shown that the RNA-binding protein HuR increases the half-life of some messenger RNAs that contain adenylate/uridylate-rich decay elements [32].
• Gel filtration and enzyme activity assays confirmed that the hexamer is the active form for nsp15 and demonstrate the specificity of nsp15 for uridylate [33].
• The UTP-depleting action was minimal, however, at a dose of 25 mumol/kg or less, indicating that interference in uridylate metabolism will be negligible at the doses required for positron emission tomography of the liver using the 18F-labeled compound [34].
• The rapid separation of orotate, orotidylate, and uridylate by thin-layer chromatography. Utility in the assay of orotate phosphoribosyltransferase and orotidylate decarboxylase [35].

References