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91.
The 2'-O-ribose methyltransferase for cap 1 of spliced leader RNA and U1 small nuclear RNA in Trypanosoma brucei
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Zamudio JR Mittra B Foldynová-Trantírková S Zeiner GM Lukes J Bujnicki JM Sturm NR Campbell DA 《Molecular and cellular biology》2007,27(17):6084-6092
mRNA cap 1 2'-O-ribose methylation is a widespread modification that is implicated in processing, trafficking, and translational control in eukaryotic systems. The eukaryotic enzyme has yet to be identified. In kinetoplastid flagellates trans-splicing of spliced leader (SL) to polycistronic precursors conveys a hypermethylated cap 4, including a cap 0 m7G and seven additional methylations on the first 4 nucleotides, to all nuclear mRNAs. We report the first eukaryotic cap 1 2'-O-ribose methyltransferase, TbMTr1, a member of a conserved family of viral and eukaryotic enzymes. Recombinant TbMTr1 methylates the ribose of the first nucleotide of an m7G-capped substrate. Knockdowns and null mutants of TbMTr1 in Trypanosoma brucei grow normally, with loss of 2'-O-ribose methylation at cap 1 on substrate SL RNA and U1 small nuclear RNA. TbMTr1-null cells have an accumulation of cap 0 substrate without further methylation, while spliced mRNA is modified efficiently at position 4 in the absence of 2'-O-ribose methylation at position 1; downstream cap 4 methylations are independent of cap 1. Based on TbMTr1-green fluorescent protein localization, 2'-O-ribose methylation at position 1 occurs in the nucleus. Accumulation of 3'-extended SL RNA substrate indicates a delay in processing and suggests a synergistic role for cap 1 in maturation. 相似文献
92.
Dabrowska K Zembala M Boratynski J Switala-Jelen K Wietrzyk J Opolski A Szczaurska K Kujawa M Godlewska J Gorski A 《Archives of microbiology》2007,187(6):489-498
We previously investigated the biological, non-antibacterial effects of bacteriophage T4 in mammals (binding to cancer cells
in vitro and attenuating tumour growth and metastases in vivo); we selected the phage mutant HAP1 that was significantly more
effective than T4. In this study we describe a non-sense mutation in the hoc gene that differentiates bacteriophage HAP1 and its parental strain T4. We found no substantial effects of the mutation on
the mutant morphology, and its effects on electrophoretic mobility and hydrodynamic size were moderate. Only the high ionic
strength of the environment resulted in a size difference of about 10 nm between T4 and HAP1. We compared the antimetastatic
activity of the T2 phage, which does not express protein Hoc, with those of T4 and HAP1 (B16 melanoma lung colonies). We found
that HAP1 and T2 decreased metastases with equal effect, more strongly than did T4. We also investigated concentrations of
T4 and HAP1 in the murine blood, tumour (B16), spleen, liver, or muscle. We found that HAP1 was rapidly cleared from the organism,
most probably by the liver. Although HAP1 was previously defined to bind cancer cells more effectively (than T4), its rapid
elimination precluded its higher concentration in tumours.
Maria Zembala and Janusz Boratynski contributed equally to this work. 相似文献
93.
In Saccharomyces cerevisiae, a two-subunit methyltransferase (Mtase) encoded by the essential genes TRM6 and TRM61 is responsible for the formation of 1-methyladenosine, a modified nucleoside found at position 58 in tRNA that is critical for the stability of tRNA(Met)i The crystal structure of the homotetrameric m1A58 tRNA Mtase from Mycobacterium tuberculosis, TrmI, has been solved and was used as a template to build a model of the yeast m1A58 tRNA Mtase heterotetramer. We altered amino acids in TRM6 and TRM61 that were predicted to be important for the stability of the heteroligomer based on this model. Yeast strains expressing trm6 and trm61 mutants exhibited growth phenotypes indicative of reduced m1A formation. In addition, recombinant mutant enzymes had reduced in vitro Mtase activity. We demonstrate that the mutations introduced do not prevent heteroligomer formation and do not disrupt binding of the cofactor S-adenosyl-L-methionine. Instead, amino acid substitutions in either Trm6p or Trm61p destroy the ability of the yeast m1A58 tRNA Mtase to bind tRNA(Met)i, indicating that each subunit contributes to tRNA binding and suggesting a structural alteration of the substrate-binding pocket occurs when these mutations are present. 相似文献
94.
Skórzewska A Bidziński A Lehner M Turzyńska D Sobolewska A Hamed A Szyndler J Maciejak P Plaznik A 《Hormones and behavior》2007,52(3):317-325
The effects of acute pretreatment of rats with corticosterone (5 and 20 mg/kg, s.c.) on emotional behavior, expression of c-Fos protein in brain structures, and serum concentration of corticosterone were studied to model the short-term glucocorticoid-dependent changes in brain functions. Corticosterone was administered 90 min before training of a conditioned fear reaction (a freezing response), and behavioral, hormonal and immunocytochemical effects were examined 1 day later, on the test day. Pretreatment of rats with corticosterone significantly attenuated the freezing reaction in the conditioned fear test. The effect of the corticosterone was accompanied by a selective enhancement of the aversive context-induced c-Fos expression in some brain structures: the parvocellular and magnocellular neurons of the paraventricular hypothalamic nucleus (pPVN and mPVN), the medial amygdala nucleus (MeA), and the cingulate cortex, area 1 (Cg1), as well as an increase in the concentration of aversive context-induced endogenous serum glucocorticoid, 1.5 h and 10 min after the test session, respectively. It is suggested that the behavioral effects of acute pretreatment of rats with corticosterone could be due to changes in the mnemonic processes in the brain, inhibition of brain corticotropin releasing factor (CRF) synthesis, or stimulation of GABA-A receptor modulating neurosteroids synthesis. It is hypothesized that the enhanced activity of Cg1, MeA, pPVN, and mPVN, and the hypothalamic-pituitary-adrenal axis with concomitant increased serum glucocorticoid concentration, might serve to facilitate active coping behavior in a threatening situation. 相似文献
95.
Protein Prp8 interacts with several other spliceosomal proteins, snRNAs, and the pre-mRNA and thereby organizes the active site(s) of the spliceosome. The DEAD-box protein Brr2 and the GTPase Snu114 bind to the Prp8 C terminus, a region where mutations in human Prp8 are linked to the RP13 form of Retinitis pigmentosa. We show crystallographically that the C-terminal domain of yeast Prp8p exhibits a Jab1/MPN-like core known from deubiquitinating enzymes. Insertions and terminal appendices are grafted onto this core, covering a putative isopeptidase center whose metal binding site is additionally impaired. Targeted yeast-two-hybrid analyses show that the RP13-linked region in the C-terminal appendix of human Prp8 is essential for binding of human Brr2 and Snu114, and that RP13 point mutations in this fragment weaken these interactions. We conclude that the expanded Prp8 Jab1/MPN domain represents a pseudoenzyme converted into a protein-protein interaction platform and that dysfunction of this platform underlies Retinitis pigmentosa. 相似文献
96.
MOTIVATION: Protein structure comparison is a fundamental problem in structural biology and bioinformatics. Two-dimensional maps of distances between residues in the structure contain sufficient information to restore the 3D representation, while maps of contacts reveal characteristic patterns of interactions between secondary and super-secondary structures and are very attractive for visual analysis. The overlap of 2D maps of two structures can be easily calculated, providing a sensitive measure of protein structure similarity. PROTMAP2D is a software tool for calculation of contact and distance maps based on user-defined criteria, quantitative comparison of pairs or series of contact maps (e.g. alternative models of the same protein, model versus native structure, different trajectories from molecular dynamics simulations, etc.) and visualization of the results. AVAILABILITY: PROTMAP2D for Windows / Linux / MacOSX is freely available for academic users from http://genesilico.pl/protmap2d.htm 相似文献
97.
R.MvaI is a Type II restriction enzyme (REase), which specifically recognizes the pentanucleotide DNA sequence 5'-CCWGG-3' (W indicates A or T). It belongs to a family of enzymes, which recognize related sequences, including 5'-CCSGG-3' (S indicates G or C) in the case of R.BcnI, or 5'-CCNGG-3' (where N indicates any nucleoside) in the case of R.ScrFI. REases from this family hydrolyze the phosphodiester bond in the DNA between the 2nd and 3rd base in both strands, thereby generating a double strand break with 5'-protruding single nucleotides. So far, no crystal structures of REases with similar cleavage patterns have been solved. Characterization of sequence-structure-function relationships in this family would facilitate understanding of evolution of sequence specificity among REases and could aid in engineering of enzymes with new specificities. However, sequences of R.MvaI or its homologs show no significant similarity to any proteins with known structures, thus precluding straightforward comparative modeling. We used a fold recognition approach to identify a remote relationship between R.MvaI and the structure of DNA repair enzyme MutH, which belongs to the PD-(D/E)XK superfamily together with many other REases. We constructed a homology model of R.MvaI and used it to predict functionally important amino acid residues and the mode of interaction with the DNA. In particular, we predict that only one active site of R.MvaI interacts with the DNA target at a time, and the cleavage of both strands (5'-CCAGG-3' and 5'-CCTGG-3') is achieved by two independent catalytic events. The model is in good agreement with the available experimental data and will serve as a template for further analyses of R.MvaI, R.BcnI, R.ScrFI and other related enzymes. 相似文献
98.
Previtellogenic oocytes of a common cellar spider, Pholcus phalangioides, contain a single aggregation of organelles referred here to as the Balbiani body. It is a well defined ooplasmic structure predominantly composed of fine granular nuage, RNA rich material but comprising also mitochondria, vesicles of endoplasmic reticulum and stacks of Golgi cysternae. The Balbiani body originates early during previtellogenesis in the form of a cap-shaped mass in juxtaposition to one pole of the oocyte nucleus. During later stages of previtellogenic growth the Balbiani body translocates as a single body towards the ooplasm periphery. The results presented indicate that Balbiani body translocation is cytoskeleton independent. Balbiani body repositioning does not result in the localization of its components to any distinct, asymmetrically situated region of the ooplasm but, instead, ends up with their even dispersion in the oocyte cortex. The Balbiani body in Pholcus does not seem to be implicated either in germ cell determination or organelle inheritance. Its homology with similar organelle accumulations in the oocytes of other species is discussed. 相似文献
99.
Kowalska J Lewdorowicz M Zuberek J Bojarska E Stepinski J Stolarski R Darzynkiewicz E Jemielity J 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1301-1305
Enzymatic cleavage of the P-chiral diastereoisomers of the 5' mRNA cap analogue bearing phosphorothioate moiety in alfa position of 5',5'-triphosphate bridge (m(7)Gppp(S)G D1 and D2) was performed by human Decapping Scavenger (DcpS) enzyme. Analysis of the degradation products allowed to estimate the absolute configuration at the asymmetric phosphorus atoms in examined compounds via correlation with the R(P) and S(P) diastereoisomers of guanosine 5'-O-(1-thiodiphosphate) (GDPalphaS). 相似文献
100.
Darzynkiewicz ZM Bojarska E Stepinski J Jemielity J Jankowska-Anyszka M Davis RE Darzynkiewicz E 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1349-1352
Eukaryotic cells utilize scavenger decapping enzymes to degrade cap structure following 3'-5' mRNA decay. Human DcpS recently has been described as a highly specific hydrolase (a member of the HIT family) that catalyses the cleavage of m(7)GpppG and short capped oligoribonucleotides. We have demonstrated here that cap-1 (m(7)GpppGm) is a preferred substrate among several investigated dinucleotide cap analogues m(7)Gp(n)N (n = 3-5, N is a purine or pyrimidine base) and m(7)GMP is always one of the reaction product. Cap analogues containing pyrimidine base instead of guanine or diphosphate chain are resistant to hydrolysis catalyzed by human scavenger. Contrary to the other enzymes of HIT family, hDcpS activity is not stimulated by Mg(2+). 相似文献