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1.
All mRNAs on the yeast mitochondrial genome terminate at a conserved dodecamer sequence 5'-AAUAAUAUUCUU-3'. We have characterized two mutants with altered dodecamers. One contains a deletion of the dodecamer at the end of the var1 gene, and the other contains two adjacent transversions in the dodecamer at the end of the reading frame of fit1, a gene within the omega+ allele of the 21S rRNA gene. In each mutant, expression of the respective gene is blocked completely. A dominant nuclear suppressor, SUV3-1, was isolated that suppresses the var1 deletion but is without effect on the fit1 dodecamer mutations. Unexpectedly, however, we found that SUV3-1 blocks expression of the wild-type fit1 allele by blocking processing at its dodecamer. SUV3-1 has pleiotropic effects on mitochondrial gene expression, affecting RNA processing, RNA stability, and translation. Our results suggest that RNA metabolism and translation may be part of a multicomponent complex within mitochondria. 相似文献
2.
A UV-induced, Mg(2+)-dependent crosslink traps an active form of domain 3 of a self-splicing group II intron. 总被引:4,自引:0,他引:4 下载免费PDF全文
In vitro irradiation of a15 gamma group II intron RNA with low doses of 254 nm UV light induces a single major crosslink. This crosslink was mapped within the domain 3 substructure of this RNA and one of the participating nucleotides was identified. When an RNA containing only the domain 3 substructure is irradiated under the same conditions, an intramolecular crosslink forms between two specific pyrimidines, one of them identical to the nucleotide crosslinked in the full-length intron RNA. In both RNAs, the crosslink is magnesium ion-dependent and photoreversible. A trans assay for domain 3 function was developed and used to find that the crosslinked domain 3 RNA remains highly reactive. This suggests that crosslinking has trapped a functional, Mg(2+)-induced folded state of this group II intron substructure and that this folding is probably independent of the other domains of the intron. 相似文献
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Daisuke Asai Riki Toita Masaharu Murata Yoshiki Katayama Hideki Nakashima Jeong-Hun Kang 《FEBS letters》2014
G protein-coupled receptor kinases (GRKs) control the signaling and activation of G protein-coupled receptors through phosphorylation. In this study, consensus substrate motifs for GRK2 were identified from the sequences of GRK2 protein substrates, and 17 candidate peptides were synthesized to identify peptide substrates with high affinity for GRK2. GRK2 appears to require an acidic amino acid at the −2, −3, or −4 positions and its consensus phosphorylation site motifs were identified as (D/E)X1–3(S/T), (D/E)X1–3(S/T)(D/E), or (D/E)X0–2(D/E)(S/T). Among the 17 peptide substrates examined, a 13-amino-acid peptide fragment of β-tubulin (DEMEFTEAESNMN) showed the highest affinity for GRK2 (Km, 33.9 μM; Vmax, 0.35 pmol min−1 mg−1), but very low affinity for GRK5. This peptide may be a useful tool for investigating cellular signaling pathways regulated by GRK2. 相似文献
6.
Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin 总被引:4,自引:0,他引:4
Nachmias B Lazar I Elmalech M Abed-El-Rahaman I Asshab Y Mandelboim O Perlman R Ben-Yehuda D 《Apoptosis : an international journal on programmed cell death》2007,12(7):1129-1142
Livin is a member of the Inhibitor of Apoptosis Protein family which inhibits apoptosis induced by a variety of stimuli. We
previously identified Livin and demonstrated that following apoptotic stimuli, Livin is cleaved by effector caspases to produce
a truncated form with paradoxical pro-apoptotic activity. In the present study, we reveal that while full-length Livin shows
diffuse cytoplasmic localization, truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization
to the Golgi apparatus. Using mutation analysis, we identified two domains that are crucial for the pro-apoptotic activity
of tLivin: the N-terminal region of tLivin which is exposed by cleavage, and the RING domain. We demonstrate that, of the
N-terminal sequence, only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin. However,
while the perinuclear localization of tLivin is essential, it is not sufficient for tLivin to exert its pro-apoptotic function.
Once tLivin is properly localized, an intact RING domain enables its pro-apoptotic function.
Electronic Supplementary Material Supplementary material is available in the online version of this article at . 相似文献
7.
Pentamidine inhibits mitochondrial intron splicing and translation in Saccharomyces cerevisiae 总被引:3,自引:0,他引:3 下载免费PDF全文
Pentamidine inhibits in vitro splicing of nuclear group I introns from rRNA genes of some pathogenic fungi and is known to inhibit mitochondrial function in yeast. Here we report that pentamidine inhibits the self-splicing of three group I and two group II introns of yeast mitochondria. Comparison of yeast strains with different configurations of mitochondrial introns (12, 5, 4, or 0 introns) revealed that strains with the most introns were the most sensitive to growth inhibition by pentamidine on glycerol medium. Analysis of blots of RNA from yeast strains grown in raffinose medium in the presence or absence of pentamidine revealed that the splicing of seven group I and two group II introns that have intron reading frames was inhibited by the drug to varying extents. Three introns without reading frames were unaffected by the drug in vivo, and two of these were inhibited in vitro, implying that the drug affects splicing by acting directly on RNA in vitro, but on another target in vivo. Because the most sensitive introns in vivo are the ones whose splicing depends on a maturase encoded by the intron reading frames, we tested pentamidine for effects on mitochondrial translation. We found that the drug inhibits mitochondrial but not cytoplasmic translation in cells at concentrations that inhibit mitochondrial intron splicing. Therefore, pentamidine is a potent and specific inhibitor of mitochondrial translation, and this effect explains most or all of its effects on respiratory growth and on in vivo splicing of mitochondrial introns. 相似文献
8.
Endocytosis in the retinal pigment epithelium (RPE) of rats was studied using horseradish peroxidase, microperoxidase and ferritin tracers. Tracer uptake was mediated by coated pits and coated vesicles. Coated pits formed at two discrete regions at the RPE plasma membrane: that portion of basal membrane directly opposing Bruch's membrane, and at the bases of the apical lamellae and villi. Two populations of coated vesicles were identified and distinguished by size, location and function. Large coated vesicles (91.8 +/- 14.7 nm in diameter) were located near the cell surface and incorporated tracer. Small coated vesicles (64.5 +/- 15.7 nm diameter) located more deeply within the cell were not tracer-labeled, and were often fused with the endoplasmic reticulum or the Golgi apparatus. Observations of the endocytic pathway in rat RPE cells are presented. Tracer was also found in organelles of the lysosomal system, e.g. the multivesicular body, but was not identified in the smooth endoplasmic reticulum or Golgi apparatus. 相似文献
9.
Riki Kawaguchi Ming Zhong Miki Kassai Mariam Ter-Stepanian Hui Sun 《The Journal of membrane biology》2013,246(8):647-660
Retinoids are vitamin A derivatives with diverse biological functions. Both natural and artificial retinoids have been used as therapeutic reagents to treat human diseases, but not all retinoid actions are understood mechanistically. Plasma retinol binding protein (RBP) is the principal and specific carrier of vitamin A in the blood. STRA6 is the membrane receptor for RBP that mediates cellular vitamin A uptake. The effects of retinoids or related compounds on the receptor’s vitamin A uptake activity and its catalytic activities are not well understood. In this study, we dissected the membrane receptor-mediated vitamin A uptake mechanism using various retinoids. We show that a subset of retinoids strongly stimulates STRA6-mediated vitamin A release from holo-RBP. STRA6 also catalyzes the exchange of retinol in RBP with certain retinoids. The effect of retinoids on STRA6 is highly isomer-specific. This study provides unique insights into the RBP receptor’s mechanism and reveals that the vitamin A transport machinery can be a target of retinoid-based drugs. 相似文献
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