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At least 595 records · Page 33Linked to original sources
PubMed1998

Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast.

The messenger RNA 3' poly(A) tail critically affects the initiation and control of translation in eukaryotes. By analogy to elements involved in transcription initiation, the poly(A) tail has been described as a 'translational enhancer' that enhances the 'translational promoter' activity of the mRNA 5'-cap structure. Elongation or shortening of the poly(A) tail regulates translation during development. Here we show, using cell-free and in vivo translation analyses in Saccharomyces cerevisiae, that the poly(A) tail can act as an independent 'translational promoter', delivering ribosomes to uncapped mRNAs even if their 5' end is blocked. When mRNAs compete for ribosome binding, neither the cap structure nor the poly(A) tail alone is enough to drive efficient translation, but together they synergize and direct ribosome entry to the 5' end. The cap structure both promotes ribosome recruitment, together with the poly(A) tail, and tethers recruited ribosomes to the 5' end. Correct choice of translation initiation codons and the function of translational regulators acting on the 5' untranslated region are thus ensured by the functional interaction of the poly(A) tail with the cap structure.

Base Sequence↗
PubMed2005

The tail structure of bacteriophage T4 and its mechanism of contraction.

Bacteriophage T4 and related viruses have a contractile tail that serves as an efficient mechanical device for infecting bacteria. A three-dimensional cryo-EM reconstruction of the mature T4 tail assembly at 15-A resolution shows the hexagonal dome-shaped baseplate, the extended contractile sheath, the long tail fibers attached to the baseplate and the collar formed by six whiskers that interact with the long tail fibers. Comparison with the structure of the contracted tail shows that tail contraction is associated with a substantial rearrangement of the domains within the sheath protein and results in shortening of the sheath to about one-third of its original length. During contraction, the tail tube extends beneath the baseplate by about one-half of its total length and rotates by 345 degrees , allowing it to cross the host's periplasmic space.

Bacteriophage T4↗
PubMed2000

Host factor Hfq of Escherichia coli stimulates elongation of poly(A) tails by poly(A) polymerase I.

Current evidence suggests that the length of poly(A) tails of bacterial mRNAs result from a competition between poly(A) polymerase and exoribonucleases that attack the 3' ends of RNAs. Here, we show that host factor Hfq is also involved in poly(A) tail metabolism. Inactivation of the hfq gene reduces the length of poly(A) tails synthesized at the 3' end of the rpsO mRNA by poly(A) polymerase I in vivo. In vitro, Hfq stimulates synthesis of long tails by poly(A) polymerase I. The strong binding of Hfq to oligoadenylated RNA probably explains why it stimulates elongation of primers that already harbor tails of 20-35 A. Polyadenylation becomes processive in the presence of Hfq. The similar properties of Hfq and the PABPII poly(A) binding protein, which stimulates poly(A) tail elongation in mammals, indicates that similar mechanisms control poly(A) tail synthesis in prokaryotes and eukaryotes.

Carrier Proteins↗
PubMed2005

Gelsolin mediates calcium-dependent disassembly of Listeria actin tails.

The role of intracellular Ca2+ in the regulation of actin filament assembly and disassembly has not been clearly defined. We show that reduction of intracellular free Ca2+ concentration ([Ca2+]i) to <40 nM in Listeria monocytogenes-infected, EGFP-actin-transfected Madin-Darby canine kidney cells results in a 3-fold lengthening of actin filament tails. This increase in tail length is the consequence of marked slowing of the actin filament disassembly rate, without a significant change in assembly rate. The Ca2+-sensitive actin-severing protein gelsolin concentrates in the Listeria rocket tails at normal resting [Ca2+]i and disassociates from the tails when [Ca2+]i is lowered. Reduction in [Ca2+]i also blocks the severing activity of gelsolin, but not actin-depolymerizing factor (ADF)/cofilin microinjected into Listeria-infected cells. In Xenopus extracts, Listeria tail lengths are also calcium-sensitive, markedly shortening on addition of calcium. Immunodepletion of gelsolin, but not Xenopus ADF/cofilin, eliminates calcium-sensitive actin-filament shortening. Listeria tail length is also calcium-insensitive in gelsolin-null mouse embryo fibroblasts. We conclude that gelsolin is the primary Ca2+-sensitive actin filament recycling protein in the cell and is capable of enhancing Listeria actin tail disassembly at normal resting [Ca2+]i (145 nM). These experiments illustrate the unique and complementary functions of gelsolin and ADF/cofilin in the recycling of actin filaments.

Actin Depolymerizing Factors↗
PubMed2007

The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module.

The catalytic activities of eukaryotic protein kinases (EPKs) are regulated by movement of the C-helix, movement of the N and C lobes upon ATP binding, and movement of the activation loop upon phosphorylation. Statistical analysis of the selective constraints associated with AGC kinase functional divergence reveals conserved interactions between these regulatory regions and three regions of the C-terminal tail (C-tail): the N-lobe tether (NLT), the active-site tether (AST), and the C-lobe tether (CLT). The NLT serves as a docking site for an upstream kinase PDK1 and, upon activation, positions the C-helix within the ATP binding pocket. The AST directly interacts with the ATP binding pocket, and the CLT interacts with the interlobe linker and the alphaC-beta4 loop, which appears to serve as a hinge for C-helix movement. The C-tail is a hallmark of AGC functional divergence inasmuch as most of the conserved core residues that distinguish AGC kinases from other EPKs are associated with the NLT, AST, or CLT. Moreover, several AGC catalytic core conserved residues that interact with the C-tail strikingly diverge from the canonical residues observed at corresponding positions in nearly all other EPKs, suggesting that the catalytic core may have coevolved with the C-tail in AGC kinases. These observations, along with the fact that the C-tail is needed for catalytic activity suggests that the C-tail is a cis-acting regulatory module that can also serve as a regulatory "handle," to which trans-acting cellular components can bind to modulate activity.

Amino Acid Sequence↗
PubMed1998

Cytoskeletal interactions with the leukocyte integrin beta2 cytoplasmic tail. Activation-dependent regulation of associations with talin and alpha-actinin.

Circulating leukocytes are nonadherent but bind tightly to endothelial cells following activation. The increased avidity of leukocyte integrins for endothelial ligands following activation is regulated, in part, by interaction of the beta2 subunit cytoplasmic tail with the actin cytoskeleton. We propose a mechanism to explain how tethering of the actin cytoskeleton to leukocyte integrins is regulated. In resting leukocytes, beta2 integrins are constitutively linked to the actin cytoskeleton via the protein talin. Activation of cells induces proteolysis of talin and dissociation from the beta2 tail. This phase is transient, however, and is followed by reattachment of actin filaments to integrins that is mediated by the protein alpha-actinin. The association of alpha-actinin with integrins may stabilize the cytoskeleton and promote firm adhesion to and migration across the endothelium. Glutathione S-transferase-beta2 tail fusion protein/mutagenesis experiments suggest that the affinity of alpha-actinin binding to the beta2 tail is regulated by a change in the conformation of the tail that unmasks a cryptic alpha-actinin binding domain. Positive and inhibitory domains within the beta2 tail regulate alpha-actinin binding: a single 11-amino acid region (residues 736-746) is necessary and sufficient for alpha-actinin binding, and a regulatory domain between residues 748-762 inhibits constitutive association of the beta2 tail with alpha-actinin.

Actinin↗
PubMed1999

DnaB from Thermus aquaticus unwinds forked duplex DNA with an asymmetric tail length dependence.

DnaB helicase is a ring-shaped hexamer of 300 kDa that is essential for replication of the bacterial chromosome. The dnaB gene from Thermus aquaticus was isolated and cloned, and its gene product was expressed and purified to homogeneity. A helicase assay was developed, and optimal conditions for T. aquaticus DnaB activity were determined using a forked duplex DNA substrate. The activity required a hydrolyzable nucleoside triphosphate and both 5'- and 3'-single-stranded DNA tail regions. Under conditions of single enzymatic turnover, the lengths of the 5'- and 3'-single-stranded regions were varied, and 6-10 nucleotides of the 5'-single-stranded tail and 21-30 nucleotides of the 3'-single-stranded tail markedly stimulated the unwinding rate. These data suggest that DnaB from T. aquaticus interacts with both DNA single-stranded tails during unwinding and that a greater portion of the 3'-tail is in contact with the protein. Two models are consistent with these data. In one model, the 5'-single stranded region passes through the central hole of the DnaB ring, and the 3'-tail makes extensive contact with the outside of the protein. In the other model, the 3'-single-stranded region passes through the DnaB ring, and the outside of the protein contacts the 5'-tail.

Bacterial Proteins↗
PubMed2000

The accessibility of histone H3 tails in chromatin modulates their acetylation by P300/CBP-associated factor.

P300/CBP-associated factor (PCAF) is a transcriptional coactivator with intrinsic histone acetylase activity. Reversible acetylation of the core histone tails in chromatin has been linked to transcriptional regulation. Here we investigate the mechanism whereby PCAF acetylates its target in chromatin. We demonstrate that recombinant PACF preferentially acetylates the H3 tail in oligonucleosomes, as compared with nucleosome core particles. The rate of acetylation is directly related to the length of the oligonucleosomal substrate. Using a trypsin accessibility assay, we demonstrate that the rate of acetylation is also related to the accessibility of the H3 tail in uncondensed oligonucleosomes. We suggest that PCAF, and perhaps other histone acetyltransferases, acetylate chromatin templates more efficiently than core particle subunits and that this preference arises from an increased accessibility of the H3 tail in either condensed or uncondensed oligonucleosomes. Acetylation of the H3 tails by the native PCAF complex is not affected by the length of the oligonucleosomal substrate. Our results suggest that the accessibility of the H3 tail in chromatin is a major factor affecting their rate of acetylation and that component(s) in the native PCAF complex function to modify the organization of these tails in chromatin thereby enhancing their accessibility to PCAF.

Acetylation↗
PubMed2000

Distant downstream sequence determinants can control N-tail translocation during protein insertion into the endoplasmic reticulum membrane.

We have studied the membrane insertion of ProW, an Escherichia coli inner membrane protein with seven transmembrane segments and a large periplasmic N-terminal tail, into endoplasmic reticulum (ER)-derived dog pancreas microsomes. Strikingly, significant levels of N-tail translocation is seen only when a minimum of four of the transmembrane segments are present; for constructs with fewer transmembrane segments, the N-tail remains mostly nontranslocated and the majority of the molecules adopt an "inverted" topology where normally nontranslocated parts are translocated and vice versa. N-tail translocation can also be promoted by shortening of the N-tail and by the addition of positively charged residues immediately downstream of the first trasnmembrane segment. We conclude that as many as four consecutive transmembrane segments may be collectively involved in determining membrane protein topology in the ER and that the effects of downstream sequence determinants may vary depending on the size and charge of the N-tail. We also provide evidence to suggest that the ProW N-tail is translocated across the ER membrane in a C-to-N-terminal direction.

ATP-Binding Cassette Transporters↗
PubMed2003

Phosphorylation of the head domain of neurofilament protein (NF-M): a factor regulating topographic phosphorylation of NF-M tail domain KSP sites in neurons.

In neurons the phosphorylation of neurofilament (NF) proteins NF-M and NF-H is topographically regulated. Although kinases and NF subunits are synthesized in cell bodies, extensive phosphorylation of the KSP repeats in tail domains of NF-M and NF-H occurs primarily in axons. The nature of this regulation, however, is not understood. As obligate heteropolymers, NF assembly requires interactions between the core NF-L with NF-M or NF-H subunits, a process inhibited by NF head domain phosphorylation. Phosphorylation of head domains at protein kinase A (PKA)-specific sites seems to occur transiently in cell bodies after NF subunit synthesis. We have proposed that transient phosphorylation of head domains prevents NF assembly in the soma and inhibits tail domain phosphorylation; i.e. assembly and KSP phosphorylation in axons depends on prior dephosphorylation of head domain sites. Deregulation of this process leads to pathological accumulations of phosphorylated NFs in the soma as seen in some neurodegenerative disorders. To test this hypothesis, we studied the effect of PKA phosphorylation of the NF-M head domain on phosphorylation of tail domain KSP sites. In rat cortical neurons we showed that head domain phosphorylation of endogenous NF-M by forskolin-activated PKA inhibits NF-M tail domain phosphorylation. To demonstrate the site specificity of PKA phosphorylation and its effect on tail domain phosphorylation, we transfected NIH3T3 cells with NF-M mutated at PKA-specific head domain serine residues. Epidermal growth factor stimulation of cells with mutant NF-M in the presence of forskolin exhibited no inhibition of NF-tail domain phosphorylation compared with the wild type NF-M-transfected cells. This is consistent with our hypothesis that transient phosphorylation of NF-M head domains inhibits tail domain phosphorylation and suggests this as one of several mechanisms underlying topographic regulation.

3T3 Cells↗
PubMed2004

A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP).

Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor sequestration through interactions, mainly with the C-terminal intracellular tails of the receptors. A library of tails from 59 representative members of the super family of seven-transmembrane receptors was probed as glutathione S-transferase fusion proteins for interactions with four different adaptor proteins previously proposed to be involved in post-endocytotic sorting of receptors. Of the two proteins suggested to target receptors for recycling to the cell membrane, which is the route believed to be taken by a majority of receptors, ERM (ezrin-radixin-moesin)-binding phosphoprotein 50 (EBP50) bound only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein-coupled receptor-associated sorting protein bound 23 of the 59 tail proteins. Surface plasmon resonance analysis of the binding kinetics of selected hits from the glutathione S-transferase pull-down experiments, i.e. the tails of the virally encoded receptor US28 and the delta-opioid receptor, confirmed the expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1) receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded that the tail library provides useful information on the general importance of certain adaptor proteins, for example, in this case, ruling out EBP50 as being a broad spectrum-recycling adaptor.

Amino Acid Sequence↗
PubMed2004

Artificial inoculation-perspectives in tailings phytostabilization.

Intensive mining and processing activities worldwide resulted in the generation of huge amounts of waste (tailings), generally characterized as toxic, radioactive, and/or hazardous. The exposure potential and, hence, the risk posed by such wastes is enhanced by a general lack of vegetation. Phytostabilization has proven to be efficient in reducing this risk. However, establishing vegetation on tailing dumps may be expensive due to the intensive use of amendments and chemical fertilizers. In this article, investigations on artificial inoculation of mine tailings with bacterial strains as a means to improve the development of vegetative covers and reduce application cost by eliminating chemical fertilization are presented and discussed. The development of plants and microbial communities from tailings, as well as the impact of inoculation on metal uptake in plants, were studied. Experiments were carried out in greenhouse using two types of mine tailings (phosphogypsum and sulphidic tailings) from the Romanian Black Sea coast. Indigenous herbaceous plants were cultivated on tailings with the addition of chemical fertilizers versus bacterial inoculation. After a 6-month experimental period, excellent plant growth, which is associated with a rich microbial community, was observed in all inoculated treatments, in contrast with poor plant growth and microbiota from the chemical fertilization treatments alone. Additionally, artificial inoculation improved plant resistance to heavy metals by reducing the uptake of some toxic metals. Once a rich microbial community is established, inoculation may be discontinued. Based on these results, efficient and cost-effective phytostabilization schemes can be proposed.

Azotobacter↗
PubMed2003

The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate.

The phosphorylated carboxyl-terminal "tail" domains of the neurofilament (NF) subunits, NF heavy (NF-H) and NF medium (NF-M) subunits, have been proposed to regulate axon radial growth, neurofilament spacing, and neurofilament transport rate, but direct in vivo evidence is lacking. Because deletion of the tail domain of NF-H did not alter these axonal properties (Rao, M.V., M.L. Garcia, Y. Miyazaki, T. Gotow, A. Yuan, S. Mattina, C.M. Ward, N.S. Calcutt, Y. Uchiyama, R.A. Nixon, and D.W. Cleveland. 2002. J. Cell Biol. 158:681-693), we investigated possible functions of the NF-M tail domain by constructing NF-M tail-deleted (NF-MtailDelta) mutant mice using an embryonic stem cell-mediated "gene knockin" approach that preserves normal ratios of the three neurofilament subunits. Mutant NF-MtailDelta mice exhibited severely inhibited radial growth of both motor and sensory axons. Caliber reduction was accompanied by reduced spacing between neurofilaments and loss of long cross-bridges with no change in neurofilament protein content. These observations define distinctive functions of the NF-M tail in regulating axon caliber by modulating the organization of the neurofilament network within axons. Surprisingly, the average rate of axonal transport of neurofilaments was unaltered despite these substantial effects on axon morphology. These results demonstrate that NF-M tail-mediated interactions of neurofilaments, independent of NF transport rate, are critical determinants of the size and cytoskeletal architecture of axons, and are mediated, in part, by the highly phosphorylated tail domain of NF-M.

Animals↗
PubMed2006

The C-terminal tail of mitochondrial transcription factor a markedly strengthens its general binding to DNA.

Mitochondrial transcription factor A (TFAM) contains a basic C-terminal tail which is essential for the promoter-specific transcription. TFAM is also a major component of a protein-mitochondrial DNA (mtDNA) complex, called nucleoid, as a non-specific DNA-binding protein. However, little is known about a role of the C-tail in the nucleoid. Overexpression of full-length TFAM decreased the amount of a D-loop form of mtDNA in cells, while overexpression of TFAM lacking its C-tail (TFAM-DeltaC) did not, suggesting that the C-tail is involved in destabilization or formation of the D-loop. An mRNA for mtDNA-derived ND1 was hardly decreased in the former but rather decreased in the latter. Given that the D-loop formation is coupled with the transcription, the decrease in the D-loop is likely due to its destabilization. The recombinant full-length TFAM much strongly unwound DNA than TFAM-DeltaC, which is consistent with the above idea because D-loop is resolved by unwinding of the supercoiling state. Notably, truncation of the C-tail decreased DNA-binding activity of TFAM by three orders of magnitude. Thus, the C-terminal tail of TFAM is important for the strong general binding to mtDNA. This strong DNA-binding conferred by the C-tail may play an important role in the nucleoid structure.

DNA, Mitochondrial↗
PubMed1996

Management of adenocarcinoma of the body and tail of the pancreas.

OBJECTIVE: The authors examined the resectability, operative morbidity mortality, and survival of patients with pancreatic adenocarcinoma of the body and tail compared with lesions in the head. SUMMARY BACKGROUND DATA: Adenocarcinoma of the body and tail of the pancreas is characteristically thought of as a disease that presents late and rarely is operable or resectable. METHODS: In an 11-year period, 1981 patients were admitted and entered into a prospective database at Memorial Sloan-Kettering Cancer Center with a diagnosis of peripancreatic cancer, 1363 of whom had adenocarcinoma of the pancreas, 75% with lesions in the head and 25% with lesions in the body and tail. RESULTS: Of 271 patients resected, 237 (23%) had lesions in the head and 34 (10%) had body and tail lesions. Perioperative mortality was 4% for patients with pancreatic lesions in the head and 0% for patients with pancreatic lesions in the body and tail. Five-year actuarial survival for body and tail lesions was projected at 14% for 5 years. Actual survival was 19%, with three patients alive for more than 5 years. CONCLUSIONS: Adenocarcinoma of the body and tail of the pancreas, although less likely to be resectable at presentation than lesions in the pancreatic head, have similar postresection survival.

Adenocarcinoma↗
PubMed1991

Abandoned Rayrock uranium mill tailings in the Northwest Territories: environmental conditions and radiological impact.

Field and laboratory investigations were undertaken of the environment surrounding abandoned U mill tailings at Rayrock, Northwest Territories, Canada, to examine the extent of 226Ra and U contamination. Samples of ground water, surface water, and unconsolidated geological material from the Rayrock area were collected for chemical and radiochemical analyses. Results indicated that the surface waters contained levels of 226Ra as high as 20 Bq L-1, 210Pb as high as 1.1 Bq L-1, and ground water U as high as 2800 micrograms L-1. Lower levels of 226Ra, 210Pb, and U, 3.6 Bq L-1, 0.5 Bq L-1, and 4 micrograms L-1, respectively, were found in a small lake adjacent to the tailings area. Analysis of tailings and soil in the immediate vicinity indicates that the radionuclides and U are mobilized and can move within the tailings. Some of the mobilized radionuclides will be bound by the surrounding peat. The remainder may move to Lake Alpha in ground water. Surface water flow also transports some contaminants both in the water of Alpha Creek and by washing tailings into Lake Alpha. The potential annual external and internal dose equivalents to a hypothetical resident were calculated based on exposure from the abandoned U mill tailings, drinking water, and fish caught in the lakes in the vicinity of the tailings. While Alpha Creek and Lake Alpha water showed evidence of contamination, the rest of the water system and the fish were at natural background levels of radioactivity.

Animals↗
PubMed2005

Part of the C-terminal tail of the envelope gp41 transmembrane glycoprotein of human immunodeficiency virus type 1 is exposed on the surface of infected cells and is involved in virus-mediated cell fusion.

The C-terminal tail of the gp41 transmembrane glycoprotein of the human immunodeficiency virus type 1 (HIV-1) virion is usually thought to be inside the virion, but it has been shown recently that part of the tail is exposed on the virion exterior. Here, using a panel of antibodies, it was demonstrated that the same part of the tail is exposed on the surface of HIV-1-infected C8166 lymphoblastoid cells and HeLa cells infected with a gp41-expressing vaccinia virus recombinant. Both types of infected cell failed to react with p17 matrix protein-specific IgGs until permeabilized with saponin, confirming the integrity of the plasma membrane. Cell-surface exposure of the gp41 tail was independently demonstrated by inhibition of HIV-1-mediated cell-cell fusion by one of the gp41 tail-specific antibodies. These data also implicate the exposed region of the gp41 C-terminal tail either directly or indirectly in the viral fusion process. Its surface exposure suggests that the gp41 C-terminal tail may be a candidate for immune intervention or chemotherapy of infection.

Cell Fusion↗
PubMed1991

The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency.

The cap structure and the poly(A) tail are important regulatory determinants in establishing the translational efficiency of a messenger RNA. Although the mechanism by which either determinant functions remains poorly characterized, the interaction between the poly(A) tail-poly(A)-binding protein complex and events occurring at the 5' terminus during translation initiation has been an intriguing possibility. In this report, the mutual dependence of the cap and the poly(A) tail was studied. Poly(A)+ and poly(A)- luciferase (Luc) mRNAs generated in vitro containing or lacking a cap were translated in vivo in tobacco protoplasts, Chinese hamster ovary cells, and yeast following delivery by electroporation. The poly(A) tail-mediated regulation of translational efficiency was wholly dependent on the cap for function. Moreover, cap function was enhanced over an order of magnitude by the presence of a poly(A) tail. The relative differences in stability between the mRNAs could not account for the synergism. The synergism between the cap and poly(A) tail was not observed in yeast cells in which active translation had been disrupted. In addition, the synergism was not observed in in vitro translation lysates. These data demonstrate that the cap and the poly(A) tail are interdependent for optimal function in vivo and suggest that communication between the two regulatory determinants may be important in establishing efficient translation.

Animals↗