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Query: UNIPROT:P06889 (Mol)
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The structures of poly(dA-dT), poly(dA-dBr5U) and of poly(dA).poly(dT) have been investigated in solution and in fibers, by Raman spectroscopy. Both the alternating poly(dA-dT), poly(dA-dBr5U) and non-alternating poly(dA).poly(dT) exhibit, in the region of sugar phosphate backbone vibrations, two bands of almost equal intensity at about 841 cm-1 and 817 cm-1. The analysis of the characteristic bands of thymine residues that are sensitive to sugar puckers gives indication of a significant displacement from the C(2')-endo conformer suggesting the adoption of alternative conformers such as O(4')-endo. In contrast, the diagnostic Raman bands for the sugar pucker of adenine residues suggest, instead, predominant adoption of C(2')-endo conformations. These Raman results are compatible with rapid dynamic changes of sugar puckers between C(2')-endo and O(4')-endo for the thymidine (and uridine) residues, whereas in adenine residues the sugar puckers fluctuate around the C(2')-endo pucker in all synthetic DNA molecules studied. Molecular dynamics simulations, performed on six different starting models using two distance-dependent dielectric functions epsilon(r) = 4 r and a sigmoidal dependence), all gave similar dynamic behavior in agreement with these Raman data and their interpretation. The mean calculated pseudorotation phases of the adenine residues are systematically higher (around C(2')-endo) than those of the thymine residues (close to O(4')-endo-C(1')-exo). Besides, the mean lifetimes of the thymine residues are 1.5 to 2.0-fold higher in the O(4')-endo than in the C(2')-endo domain, while those of the adenine residues are two to threefold higher in the C(2')-endo than in the O(4')-endo domain. In the Raman spectra of the alternating poly(dA-dBr5U), the splitting of a band into two components arising from the two contributions of ApBr5U and Br5UpA provides strong evidence for a repeating dinucleotide structure in solution. The calculated twist values averaged over the simulation runs are also systematically higher in the 5'T-A3' step (39 degrees) than in the 5'A-T3' step (33 degrees). Simultaneously, the calculated roll values are positive in the 5'T-A3' step (6 degrees) and negative in the 5'A-T3' step (-9 degrees), while the propeller twist values are about the same (-11 degrees to -16 degrees). On the other hand, in the homopolymer, the average twist value is close to 36 degrees with the roll angle close to 0 degrees and large propeller twist values (-20 degrees).
J Mol Biol 1992 Jan 20
PMID:Investigations on the dynamic structures of adenine- and thymine-containing DNA. 173 58

The URA7 gene of Saccharomyces cerevisiae encodes CTP synthetase (EC 6.3.4.2) which catalyses the conversion of uridine 5'-triphosphate to cytidine 5'-triphosphate, the last step of the pyrimidine biosynthetic pathway. We have cloned and sequenced the URA7 gene. The coding region is 1710 bp long and the deduced protein sequence shows a strong degree of homology with bacterial and human CTP synthetases. Gene disruption shows that URA7 is not an essential gene: the level of the intracellular CTP pool is roughly the same in the deleted and the wild-type strains, suggesting that an alternative pathway for CTP synthesis exists in yeast. This could involve either a divergent duplicated gene or a different route beginning with the amination of uridine mono- or diphosphate.
Mol Gen Genet 1991 Dec
PMID:Cloning, sequencing and characterization of the Saccharomyces cerevisiae URA7 gene encoding CTP synthetase. 175 46

The hypermodified base 2-methylthio-N6-isopentenyladenosine (ms2i6A) at position 37 occurs frequently in tRNAs that read codons starting with uridine. Here we have studied how ms2i6A affects the accuracy of poly(U) translation in vitro. Deficiency leads to a higher rejection rate of tRNA4(Leu) by more aggressive proofreading on the wild-type ribosome, but with the initial selection step unchanged. Our data indicate that ms2i6A has no effect on codon-anticodon interactions on wild-type ribosomes as long as aminoacyl-tRNA is in ternary complex with EF-Tu and GTP. ms2i6A deficiency in the cognate poly(U) reader tRNA(Phe) leads to increased misreading when the near-cognate competitor tRNA4(Leu) is wild-type. ms2i6A deficiency in tRNA4(Leu) gives a decreased error level in competition with wild-type tRNA(Phe).
J Mol Biol 1991 Dec 20
PMID:ms2i6A deficiency enhances proofreading in translation. 176 49

The transport of thymidine by the protozoan parasite Giardia intestinalis was examined at 0 degrees C. This temperature prevented attachment of the cells to vessel walls, so that a rapid sampling technique could be used. Thymidine influx (distinguished from gross uptake) was readily measurable at 0 degrees C and was specific and saturable. The transporter appears to be a facilitative carrier, exhibiting a high affinity for thymidine (Km = 50 microM). Thymine and uracil were the most effective inhibitors (Ki = 30 microM and 45 microM, respectively), followed by thymidine, deoxyuridine and uridine (Ki = 64-96 microM). Cytosine, cytidine and deoxycytidine were not inhibitory, even at high concentrations. The data indicate that the oxygen at position 4 of the pyrimidine ring is essential for recognition by the transporter, whereas the 5-methyl group of thymine is unimportant. The furanose ring appears not to be recognized, since D-ribose was non-inhibitory and uridine and deoxyuridine were equally inhibitory but less so than uracil and thymine. This carrier probably mediates the transport of uracil, as well as uridine and thymidine, although influx of the base remains to be measured.
Mol Biochem Parasitol 1991 Oct
PMID:Characteristics of thymidine transport in Giardia intestinalis trophozoites. 176 28

Influenza virus NS1 mRNA is spliced by host nuclear enzymes to form NS2 mRNA, and this splicing is regulated in infected cells such that the steady-state amount of spliced NS2 mRNA is only about 10% of that of unspliced NS1 mRNA. This regulation would be expected to result from a suppression in the rate of splicing coupled with the efficient transport of unspliced NS1 mRNA from the nucleus. To determine whether the rate of splicing of NS1 mRNA was controlled by trans factors in influenza virus-infected cells, the NS1 gene was inserted into an adenovirus vector. The rates of splicing of NS1 mRNA in cells infected with this vector and in influenza virus-infected cells were measured by pulse-labeling with [3H]uridine. The rates of splicing of NS1 mRNA in the two systems were not significantly different, strongly suggesting that the rate of splicing of NS1 mRNA in influenza virus-infected cells is controlled solely by cis-acting sequences in NS1 mRNA itself. In contrast to the rate of splicing, the extent of splicing of NS1 mRNA in the cells infected by the adenovirus recombinant was dramatically increased relative to that occurring in influenza virus-infected cells. This could be attributed largely, if not totally, to a block in the nucleocytoplasmic transport of unspliced NS1 mRNA in the recombinant-infected cells. Most of the unspliced NS1 mRNA was in the nuclear fraction, and no detectable NS1 protein was synthesized. When the 3' splice site of NS1 mRNA was inactivated by mutation, NS1 mRNA was transported and translated, indicating that the transport block occurred because NS1 rRNA was committed to the splicing pathway. This transport block is apparently obviated in influenza virus-infected cells. These experiments demonstrate the important role of the nucleocytoplasmic transport of unspliced NS1 mRNA in regulating the extent of splicing of NS1 mRNA.
Mol Cell Biol 1991 Feb
PMID:Regulation of the extent of splicing of influenza virus NS1 mRNA: role of the rates of splicing and of the nucleocytoplasmic transport of NS1 mRNA. 182 58

The mitochondrial DNA of trypanosomes is composed of maxicircle and minicircle DNAs catenated into a network, called the kinetoplast. Maxicircles encode proteins and RNAs necessary for mitochondrial assembly. Minicircles encode small transcripts which are believed to serve as guide RNAs in the process of RNA editing of maxicircle transcripts. Trypanosoma equiperdum minicircles contain three transcription units which produce three distinct transcripts. The genes for these transcripts are flanked by imperfect 18-bp repeats separated by approximately 110 bp. The transcripts have a 5' triphosphate, indicating that they are primary transcripts. Minicircle transcription initiates at a purine within a conserved sequence, 5'-AYAYA-3', where Y is a pyrimidine, 32 bp from the upstream inverted repeat, suggesting that the repeats may function in transcript initiation. Transcripts from a single minicircle transcription unit range in size from 55 to 70 nucleotides. This size heterogeneity within a single sequence class is due to the variable length of nontemplated uridine residues composing a 3' tail. The size range and heterogeneous polyuridylate 3' end of the minicircle transcripts appear to be conserved features and may be related to transcript function.
Mol Cell Biol 1991 Mar
PMID:Trypanosoma equiperdum minicircles encode three distinct primary transcripts which exhibit guide RNA characteristics. 182 48

Regulation of influenza virus RNA replication was studied with the use of A/FPV/Rostock/34 strain ts-mutants. Mutants C44, C15, C45 possessing the ts-defects in the PB2, PB1 and PA genes respectively were used for the infection of chick embryo cultured cells and H-uridine-labelled nucleocapsid-associated RNA was analysed in polyacrylamide gel electrophoresis to assess the kinetics of vRNA synthesis. A typical early-late transition of the pattern of vRNA synthesis was observed in the cells infected with C44, whereas the other two mutants exhibited a slightly changed (C15) or strongly distorted (C45) pattern. In shift up experiments after the transfer to non-permissive temperature all the mutants exhibited partial reversion to an early pattern of vRNA synthesis. The results are discussed in connection with the mechanism of the early-late transition of influenza virus-specific RNA synthesis.
Mol Gen Mikrobiol Virusol 1991 May
PMID:[The role of polymerase protein genes of influenza A virus in the transition from the early to late stage of replication]. 189 57

2,2,2-Triphenylethyl-UDP (TPEU) was synthesized as an analogue of the transition state of the glucuronidation reaction catalyzed by UDP-glucuronosyltransferase; it contains both a uridine and an acceptor substrate moiety. It inhibits rat liver microsomal UDP-glucuronosyltransferase [Eur. J. Biochem. 188:309-312 (1990)]. In the present work, TPEU was tested as an inhibitor of glucuronidation in intact rat hepatocytes. Two phenols (harmol and 3,3',5-triiodothyronine) and a hydroxamic acid (N-hydroxy-2-acetylaminofluorene) were used as substrates for glucuronidation. The glucuronidation of these substrates was strongly decreased by TPEU at 0.3-5 mM. Up to 5 mM TPEU did not kill the cells, as shown by unimpaired trypan blue exclusion at the end of the incubation. When glucuronidation was inhibited, the sulfation of harmol increased, as did the production of reactive species generated from N-hydroxy-2-acetylaminofluorene that bind to cellular macromolecules. This indicates that a decreased substrate consumption by loss of glucuronidation leads to increased conversion by competing pathways. The results show, therefore, that TPEU is an effective inhibitor of glucuronidation in this cellular system in vitro.
Mol Pharmacol 1991 Aug
PMID:Selective inhibition of glucuronidation by 2,2,2-triphenylethyl-UDP in isolated rat hepatocytes: conjugation of harmol, 3,3',5-triiodothyronine, and N-hydroxy-2-acetylaminofluorene. 190 49

A detailed analysis of RNA-protein complex formation in the 3' untranslated region of spinach chloroplast petD mRNA has been carried out. Five chloroplast proteins that interact with petD RNA in this region, which contains an inverted repeat sequence capable of forming a hairpin structure, have been identified. A 33-kDa protein recognizes specifically the double-stranded stem of the hairpin structure; mutations that disrupt base pairing at the base of the stem reduce or eliminate protein binding. A 57-kDa protein recognizes specifically an AU-rich sequence motif that is highly conserved in petD genes of different higher plant species. The 57-kDa protein and possibly the 33-kDa protein form stable complexes with petD RNA in vitro and may interact with each other. In addition, their interaction with petD RNA is highly sensitive to heparin. The three other proteins, of 100, 32, and 28 kDa, display little sequence or structural binding specificity apart from their preference for uridine-rich sequences. They also interact with the 3' untranslated regions of other chloroplast RNAs such as those of psbA and rbcL. The functions of these proteins in the regulation of petD gene expression, including possible roles in transcription termination and RNA stability, are discussed.
Mol Cell Biol 1991 Sep
PMID:Specific binding of chloroplast proteins in vitro to the 3' untranslated region of spinach chloroplast petD mRNA. 190 52

Ovine cumulus-enclosed oocytes collected from antral follicles (3-5 mm in diameter) were cultured in vitro with 2 x 10(6) granulosa cells/ml in the presence or absence of gonadotropins or in the presence of cytochalasin D (CD). The maturation rate was assessed after 24 h of culture. In the control group, in the presence of gonadotropins (follicle-stimulating hormone-luteinizing hormone (FSH-LH; -10 micrograms/ml) 100% of the oocytes reached metaphase II. Whereas intercellular junctions were no longer present after 6-7 h of culture, germinal vesicle breakdown (GVBD) occurred by the same time. In contrast, in the absence of gonadotropin, the majority of the oocytes (59%) remained blocked in GV stage. The inhibition exerted by the granulosa cells on meiotic resumption was overcome when the cumulus-oocyte complexes (COCs) were incubated in CD (5 micrograms/ml) for 6 h at the beginning of the culture. Under these conditions, 85% of the oocytes matured with extrusion of the first polar body. Cytological analysis by cytofluorescence (NBD phallacidin) and electron microscopy showed that, after 6 h of treatment, CD provoked a redistribution of the microfilaments, mainly in the cumulus cells and to a lesser extent in the oocyte cortex. Intercellular junctions disappeared concomitantly with a significant decrease of the intercellular transport of tritiated uridine. The initiation of GVBD occurred at the same time. These results indicate that the resumption of meiosis was correlated with a loss of both junctional complexes (intermediate and gap junctions) between the cumulus cells and the oocyte.
Mol Reprod Dev 1991 Jun
PMID:Cytochalasin D treatment induces meiotic resumption in follicular sheep oocytes. 190 84


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