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Results for “Processing Bodies”

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At least 181 records · Page 10Linked to original sources

PubMed2006

RAP55, a cytoplasmic mRNP component, represses translation in Xenopus oocytes.

mRNAs in eukaryotic cells are presumed to always associate with a set of proteins to form mRNPs. In Xenopus oocytes, a large pool of maternal mRNAs is masked from the translational apparatus as storage mRNPs. Here we identified Xenopus RAP55 (xRAP55) as a component of RNPs that associate with FRGY2, the principal component of maternal mRNPs. RAP55 is a member of the Scd6 or Lsm14 family. RAP55 localized to cytoplasmic foci in Xenopus oocytes and the processing bodies (P-bodies) in cultured human cells: in the latter cells, RAP55 is an essential constituent of the P-bodies. We isolated xRAP55-containing complexes from Xenopus oocytes and identified xRAP55-associated proteins, including a DEAD-box protein, Xp54, and a protein arginine methyltransferase, PRMT1. Recombinant xRAP55 repressed translation, together with Xp54, in an in vitro translation system. In addition, xRAP55 repressed translation in oocytes when tethered with a reporter mRNA. Domain analyses revealed that the N-terminal region of RAP55, including the Lsm domain, is important for the localization to P-bodies and translational repression. Taken together, our results suggest that xRAP55 is involved in translational repression of mRNA as a component of storage mRNPs.

Animals↗

PubMed2006

RNA granules.

Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationship between different classes of these granules and discuss how spatial organization regulates messenger RNA translation/decay.

Animals↗

PubMed2006

ZBP1 regulates mRNA stability during cellular stress.

An essential constituent of the integrated stress response (ISR) is a reversible translational suppression. This mRNA silencing occurs in distinct cytoplasmic foci called stress granules (SGs), which transiently associate with processing bodies (PBs), typically serving as mRNA decay centers. How mRNAs are protected from degradation in these structures remains elusive. We identify that Zipcode-binding protein 1 (ZBP1) regulates the cytoplasmic fate of specific mRNAs in nonstressed cells and is a key regulator of mRNA turnover during the ISR. ZBP1 association with target mRNAs in SGs was not essential for mRNA targeting to SGs. However, ZBP1 knockdown induced a selective destabilization of target mRNAs during the ISR, whereas forced expression increased mRNA stability. Our results indicate that although targeting of mRNAs to SGs is nonspecific, the stabilization of mRNAs during cellular stress requires specific protein-mRNA interactions. These retain mRNAs in SGs and prevent premature decay in PBs. Hence, mRNA-binding proteins are essential for translational adaptation during cellular stress by modulating mRNA turnover.

Animals↗

PubMed2006

ZBP1 subcellular localization and association with stress granules is controlled by its Z-DNA binding domains.

Z-DNA binding protein 1 (ZBP1) belongs to a family of proteins that contain the Zalpha domain, which binds specifically to left-handed Z-DNA and Z-RNA. Like all vertebrate proteins in the Zalpha family, it contains two Zalpha-like domains and is highly inducible by immunostimulation. Using circular dichroism spectroscopy and electrophoretic mobility shift assays we show that both Zalpha domains can bind Z-DNA independently and that substrate binding is greatly enhanced when both domains are linked. Full length ZBP1 and a prominent splice variant lacking the first Zalpha domain (DeltaZalpha) showed strikingly different subcellular localizations. While the full length protein showed a finely punctate cytoplasmatic distribution, ZBP1DeltaZalpha accumulated in large cytoplasmic granules. Mutation of residues important for Z-DNA binding in the first Zalpha domain resulted in a distribution comparable to that of ZBP1DeltaZalpha. The ZBP1DeltaZalpha granules are distinct from stress granules (SGs) and processing bodies but dynamically interacted with these. Polysome stabilization led to the disassembly of ZBP1DeltaZalpha granules, indicating that mRNA are integral components. Heat shock and arsenite exposure had opposing effects on ZBP1 isoforms: while ZBP1DeltaZalpha granules disassembled, full length ZBP1 accumulated in SGs. Our data link ZBP1 to mRNA sorting and metabolism and indicate distinct roles for ZBP1 isoforms.

Amino Acid Sequence↗

PubMed2004

Characterization of genetically labeled catecholamine neurons in the mouse retina.

Mouse neurons were labeled transgenically with red fluorescent protein (RFP) driven by the tyrosine hydroxylase (TH) promoter and observed in living retinas and brain slices. Two types of retinal amacrine cells expressed TH::RFP. One type had large cell bodies, processes that ramified in S1 of the inner plaxiform layer (IPL) and were TH immunoreactive, identifying them as dopaminergic neurons. A second type had smaller somas, ramified in S3 and lacked TH. Dopaminergic cells had large dendritic fields and exceptionally long axon-like processes, whereas type 2 cells were more compact. Neither cell type exhibited tracer coupling. Thus, murine retinal dopaminergic neurons exhibit functional anatomy similar to their primate counterparts and TH::RFP mice are useful for in situ characterization of catecholaminergic neurons.

Animals↗

PubMed2002

Bose-enhanced chemistry: amplification of selectivity in the dissociation of molecular Bose-Einstein condensates.

We study the photodissociation chemistry of a quantum degenerate gas of bosonic triatomic ABC molecules, assuming two open rearrangement channels ( AB+C or A+BC). The equations of motion are equivalent to those of a parametric multimode laser, resulting in an exponential buildup of macroscopic mode populations. By exponentially amplifying a small differential in the single-particle rate coefficients, Bose stimulation leads to a nearly complete selectivity of the collective N-body process, indicating a novel type of ultraselective quantum degenerate chemistry.

Journal Article↗

PubMed2004

Collective diffusion model for water permeation through microscopic channels.

Water permeation through nanometric channels, generally a coupled many-body process, is described in this study by a single collective coordinate. A collective diffusion model is proposed in which water movement at equilibrium is characterized as an unbiased diffusion along this coordinate and water transport in the presence of a chemical potential difference is described as one-dimensional diffusion in a linear potential. The model allows one to determine the osmotic permeability of a water channel from equilibrium simulations.

Aquaporins↗

PubMed2006

Arabidopsis DCP2, DCP1, and VARICOSE form a decapping complex required for postembryonic development.

mRNA turnover in eukaryotes involves the removal of m7GDP from the 5' end. This decapping reaction is mediated by a protein complex well characterized in yeast and human but not in plants. The function of the decapping complex in the development of multicellular organisms is also poorly understood. Here, we show that Arabidopsis thaliana DCP2 can generate from capped mRNAs, m7GDP, and 5'-phosphorylated mRNAs in vitro and that this decapping activity requires an active Nudix domain. DCP2 interacts in vitro and in vivo with DCP1 and VARICOSE (VCS), an Arabidopsis homolog of human Hedls/Ge-1. Moreover, the interacting proteins stimulate DCP2 activity, suggesting that the three proteins operate as a decapping complex. Consistent with their role in mRNA decay, DCP1, DCP2, and VCS colocalize in cytoplasmic foci, which are putative Arabidopsis processing bodies. Compared with the wild type, null mutants of DCP1, DCP2, and VCS accumulate capped mRNAs with a reduced degradation rate. These mutants also share a similar lethal phenotype at the seedling cotyledon stage, with disorganized veins, swollen root hairs, and altered epidermal cell morphology. We conclude that mRNA turnover mediated by the decapping complex is required for postembryonic development in Arabidopsis.

Arabidopsis↗

PubMed2026

Targeting the Microbiota-Gut-Brain Axis: Emerging Nanomedicine Approaches for Neurodegenerative Diseases.

The microbiota-gut-brain axis (MGBA) is a bidirectional relationship between the gut microbiota (GM) and the brain, where the GM affects the gastrointestinal tract (GIT) and the central nervous system (CNS), and vice versa. Microbiotas are important for several vital body processes, including metabolism, immunity, and homeostasis. The MGBA has three main pathways: the vagal nerve mechanism, the immune-related mechanism, and the neuroendocrine mechanism. GM imbalance, known as dysbiosis, affects the GIT, the brain, and the CNS. Furthermore, dysbiosis is linked to several neurological disorders such as Alzheimer's (AD), Parkinson's (PD), depression, autism spectrum disorder (ASD), and multiple sclerosis (MS). Studying MGBA gives researchers new therapeutic ideas using microbiota. Using special diets rich in fiber and probiotics, in addition to fecal microbiota transplantation (FMT), is being studied as a new therapy for MGBA. From the point of view that these therapeutic interventions maintain microbiota imbalance, which in turn will affect the brain and can relieve the neurological disorders caused by dysbiosis and MGBA.

Humans↗

PubMed2006

Stressed out! Effects of environmental stress on mRNA metabolism.

Exposure of yeast cells to environmental stresses can disrupt essential intracellular processes, especially those carried out by large macromolecular complexes. The production of mature, translatable mRNAs is most sensitive to stress owing to the inhibition of messenger RNA splicing and alterations in the export of mRNA from the nucleus. Changes in the cytoplasmic pools of mRNAs also occur following exposure to stress conditions. Messenger RNAs accumulate in discrete cytoplasmic foci such as processing bodies and stress granules. These dynamic changes in RNA metabolism, following exposure to stress, ensure the preferential production and export of heat-shock mRNAs and the sequestering of general cellular mRNAs in the nucleus or in cytoplasmic foci, thus allowing for a redirection of the translational machinery to encode stress proteins, which aid in cellular recovery following stress. Stress proteins, such as Hsp70p and Hsp104p, have been shown to play a direct role in the repair of macromolecular complexes involved in RNA metabolism in yeast cells, thus ensuring that the cell returns to homeostasis.

Cell Nucleus↗

PubMed2005

Inhibition of translational initiation by Let-7 MicroRNA in human cells.

MicroRNAs (miRNAs) are approximately 21-nucleotide-long RNA molecules regulating gene expression in multicellular eukaryotes. In metazoa, miRNAs act by imperfectly base-pairing with the 3' untranslated region of target messenger RNAs (mRNAs) and repressing protein accumulation by an unknown mechanism. We demonstrate that endogenous let-7 microribonucleoproteins (miRNPs) or the tethering of Argonaute (Ago) proteins to reporter mRNAs in human cells inhibit translation initiation. M(7)G-cap-independent translation is not subject to repression, suggesting that miRNPs interfere with recognition of the cap. Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression.

Argonaute Proteins↗

PubMed1984

Ultrastructural appearances of a lens with marked polychromatic lustre: evidence for diffraction as a cause.

A human lens showing polychromatic lustre associated with cortical opacities (Christmas tree cataract) has been examined by slit-lamp photography, thin-section light microscopy, and electron microscopy. Anterior epithelial cells were fibroblast-like, and an area of breakdown of cortical lens fibres was observed in the anterior lens, containing feathery fibres, whorls, and process bodies. Parallel sided stacks of fused cell membranes were found beneath the watery area at the same depth as the polychromatic lustre seen in the slit-lamp. The dimensions of these membrane plates are consistent with the diffraction of light by a parallel thin film to give coloured points of light. Deeper areas of small granules between the lens fibres are associated with the main trunk-like opacity and its branches seen with the slit-lamp.

Aged↗

PubMed1988

Physiology and pathophysiology of atrial peptides.

The atria secrete atrial peptides (atriopeptins) that are capable of producing dramatic alterations in a number of body processes. Secretion of atriopeptin appears to be regulated primarily by the prevailing pressure within the atria. In pharmacological doses, atriopeptin rapidly elicits a natriuresis when administered to experimental animals or humans. In contrast, infusion rates that increase plasma atriopeptin only by about three- to fivefold tend to produce a slowly developing and modest diuresis. Evidence examined in this review suggests that the atrial peptides are not potent natriuretic substances under normal physiological conditions, although it is likely that they exert a modulating influence on sodium excretion. The atrial peptides are vasoactive and induce a number of cardiovascular changes including decreases in arterial blood pressure, cardiac filling pressure, and cardiac output and a translocation of fluid from plasma to the interstitial fluid space. They also interact with other hormones, particularly the renin-angiotensin-aldosterone system. Finally, atriopeptin is distributed throughout many regions of the brain where it may serve as a neuromodulator or neurotransmitter. Atriopeptin circulating in the bloodstream also may influence cerebral mechanisms by acting on receptors in the circumventricular organs. A more complete understanding of the diverse effects of this cardiac endocrine system is expected to provide further insight into a spectrum of physiological and pathophysiological processes.

Animals↗

PubMed2006

Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54.

RNA interference is triggered by double-stranded RNA that is processed into small interfering RNAs (siRNAs) by Dicer enzyme. Endogenously, RNA interference triggers are created from small noncoding RNAs called microRNAs (miRNAs). RNA-induced silencing complexes (RISC) in human cells can be programmed by exogenously introduced siRNA or endogenously expressed miRNA. siRNA-programmed RISC (siRISC) silences expression by cleaving a perfectly complementary target mRNA, whereas miRNA-induced silencing complexes (miRISC) inhibits translation by binding imperfectly matched sequences in the 3' UTR of target mRNA. Both RISCs contain Argonaute2 (Ago2), which catalyzes target mRNA cleavage by siRISC and localizes to cytoplasmic mRNA processing bodies (P-bodies). Here, we show that RCK/p54, a DEAD box helicase, interacts with argonaute proteins, Ago1 and Ago2, in affinity-purified active siRISC or miRISC from human cells; directly interacts with Ago1 and Ago2 in vivo, facilitates formation of P-bodies, and is a general repressor of translation. Disrupting P-bodies by depleting Lsm1 did not affect RCK/p54 interactions with argonaute proteins and its function in miRNA-mediated translation repression. Depletion of RCK/p54 disrupted P-bodies and dispersed Ago2 throughout the cytoplasm but did not significantly affect siRNA-mediated RNA functions of RISC. Depleting RCK/p54 released general, miRNA-induced, and let-7-mediated translational repression. Therefore, we propose that translation repression is mediated by miRISC via RCK/p54 and its specificity is dictated by the miRNA sequence binding multiple copies of miRISC to complementary 3' UTR sites in the target mRNA. These studies also suggest that translation suppression by miRISC does not require P-body structures, and location of miRISC to P-bodies is the consequence of translation repression.

3' Untranslated Regions↗

PubMed1999

Measles, Hmong, and metaphor: culture change and illness management under conditions of immigration.

When 19 Hmong families and three healers in St. Paul, Minnesota, were interviewed regarding their understanding of measles and the ways in which they cared for children with the disease, their responses spanned the range between Hmong animistic cosmology and Western theories of disease. The metaphors of growth that were used to describe the disease link language, cosmology, causation, body processes, and illness management practices. This study discusses the themes of cyclical time, disease-causing spirits, the natural/supernatural dichotomy, and agricultural metaphors as applied to disease, as well as the growing adaptation to, use of, and interpretation of Western medicine by these immigrants.

Adult↗

PubMed1983

The ethnophysiology and folk dietetics of pregnancy: a case study from South India.

The contingency between notions of ethnophysiology and the folk dietetics of pregnancy are examined in a region of South India. Attention is focused on lay perceptions of essential body processes and health concerns during pregnancy. Preventive and promotive health strategies employed during pregnancy by the rural poor which involve diet are considered. The tendency for rural South Indian women to prefer smaller babies and the relationship of this preference to dietary behavior are considered in relation to both concepts of the appropriate quality and quantity of food to eat during pregnancy and the concepts of baby space and baby strength. Nutritional ramifications of alternative food consumption patterns are considered. The importance of understanding indigenous health concerns and notions of ethnophysiology when introducing public health programs is highlighted by a discussion of why many pregnant women are reluctant to comply with iron sulfate, tetanus toxoid, and vitamin therapy as currently presented by primary health care staff.

Analysis of Variance↗

PubMed1998

Axon-myelin sheath relations of oligodendrocyte unit phenotypes in the adult rat anterior medullary velum.

Axon-oligodendrocyte relations of Rip-immunolabelled and dye-injected oligodendrocyte units are characterised in the adult rat anterior medullary velum (AMV). Each oligodendrocyte unit comprised the oligodendrocyte cell body, processes and the internodal myelin segments they support. Oligodendrocyte units corresponded to classically described type I/II or type III/IV unit phenotypes which respectively myelinated discrete populations of small and large diameter axons, delineated by a myelinated fire diameter of 2-4 microns (diameter of the axon plus its myelin sheath). Within units, mean fibre diameter was directly related to mean internodal length and inversely related to the number of myelin sheaths in the unit. The relationship between fibre diameter and internodal length was retained in units which myelinated axons of different diameters, indicating that axon diameter was an important determinant of the longitudinal dimensions of myelin sheaths. We also show that type III/IV units maintained a far greater volume of myelin than type I/II units. It was concluded that type I/II and III/IV oligodendrocytes represent two functionally and morphologically distinct phenotypes whose distribution densities were determined by the diameter and spatial dispersion of axons.

Age Factors↗

PubMed2000

[Additive effect of pilocarpine and Timoptol on pupillary diameter and intraocular pressure in healthy rabbits].

In the submitted paper experimental results are interpreted comparing the administration of two fundamental anti-glaucomatous drugs into the conjunctival sac of healthy rabbits of the Chinchilla strain. The authors administered 2% pilocarpine and 0.25% Timoptol (Timololi maleas, Léciva) alone, as combined consecutive administration and concurrent administration. The greatest effect on the width of the pupil and on IOP was exerted before 60 minutes by administration of pilocarpine, then Timoptol resp. And after 60 minutes the mixture of the two substances was most effective. This effect is explained by the additive action via substances produced by interaction (metabolites). Pilocarpine being a cholinergic substance promotes formation of the vitreous fluid and thus also an increased supply of free amino acids into ciliary body processes and the vitreous fluid. Timoptol then interacts with the increased amount of free amino acids and thus a greater and longer reduction of VOT occurs than after the action of newly formed cholinergic or newly formed adrenergic substances alone.

Adrenergic beta-Antagonists↗