scholarly journals Distinct Functions of the Cap-Binding Complex in Stimulation of Nuclear mRNA Export

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Rwik Sen ◽  
Priyanka Barman ◽  
Amala Kaja ◽  
Jannatul Ferdoush ◽  
Shweta Lahudkar ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Level ◽  
Mrna Export ◽  
Mrna Splicing ◽  
Content Type ◽  
Cap Binding Complex ◽  
Cleavage And Polyadenylation ◽  
Nascent Mrna ◽  
Stimulation Of ◽  
Active Genes

ABSTRACTCap-binding complex (CBC) associates cotranscriptionally with the cap structure at the 5′ end of nascent mRNA to protect it from exonucleolytic degradation. Here, we show that CBC promotes the targeting of an mRNA export adaptor, Yra1 (forming transcription export [TREX] complex with THO and Sub2), to the active genes and enhances mRNA export inSaccharomyces cerevisiae. Likewise, recruitment of Npl3 (an hnRNP involved in mRNA export via formation of export-competent ribonuclear protein complex [RNP]) to the active genes is facilitated by CBC. Thus, CBC enhances targeting of the export factors and promotes mRNA export. Such function of CBC is not mediated via THO and Sub2 of TREX, cleavage and polyadenylation factors, or Sus1 (that regulates mRNA export via transcription export 2 [TREX-2]). However, CBC promotes splicing ofSUS1mRNA and, consequently, Sus1 protein level and mRNA export via TREX-2. Collectively, our results support the hypothesis that CBC promotes recruitment of Yra1 and Npl3 to the active genes, independently of THO, Sub2, or cleavage and polyadenylation factors, and enhances mRNA export via TREX and RNP, respectively, in addition to its role in facilitatingSUS1mRNA splicing to increase mRNA export through TREX-2, revealing distinct stimulatory functions of CBC in mRNA export.

scholarly journals The Role of Nuclear Cap Binding Protein Cbc1p of Yeast in mRNA Termination and Degradation

2000 ◽  
Vol 20 (8) ◽  
pp. 2827-2838 ◽  
Author(s):  
Biswadip Das ◽  
Zijian Guo ◽  
Patrick Russo ◽  
Pascal Chartrand ◽  
Fred Sherman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mrna Export ◽  
Degradation Pathway ◽  
The Other ◽  
Nonsense Mutations ◽  
Mrna Surveillance ◽  
Nonessential Gene ◽  
Cap Binding Complex ◽  
Low Levels

ABSTRACT The cyc1-512 mutation in Saccharomyces cerevisiae causes a 90% reduction in the level of iso-1-cytochrome c because of the lack of a proper 3′-end-forming signal, resulting in low levels of eight aberrantly longcyc1-512 mRNAs which differ in length at their 3′ termini. cyc1-512 can be suppressed by deletion of either of the nonessential genes CBC1 and CBC2, which encode the CBP80 and CBP20 subunits of the nuclear cap binding complex, respectively, or by deletion of the nonessential gene UPF1, which encodes a major component of the mRNA surveillance complex. The upf1-Δ deletion suppressed the cyc1-512defect by diminishing degradation of the longer subset ofcyc1-512 mRNAs, suggesting that downstream elements or structures occurred in the extended 3′ region, similar to the downstream elements exposed by transcripts bearing premature nonsense mutations. On the other hand, suppression of cyc1-512defects by cbc1-Δ occurred by two different mechanisms. The levels of the shorter cyc1-512 transcripts were enhanced in the cbc1-Δ mutants by promoting 3′-end formation at otherwise-weak sites, whereas the levels of the longercyc1-512 transcripts, as well as of all mRNAs, were slightly enhanced by diminishing degradation. Furthermore,cbc1-Δ greatly suppressed the degradation of mRNAs and other phenotypes of a rat7-1 strain which is defective in mRNA export. We suggest that Cbc1p defines a novel degradation pathway that acts on mRNAs partially retained in nuclei.

scholarly journals Discovery of a Novel Class of Orally Active Antifungal β-1,3-d-Glucan Synthase Inhibitors

2011 ◽  
Vol 55 (11) ◽  
pp. 5099-5106 ◽  
Author(s):  
Scott S. Walker ◽  
Yiming Xu ◽  
Ilias Triantafyllou ◽  
Michelle F. Waldman ◽  
Cara Mendrick ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Glabrata ◽  
Pharmacokinetic Data ◽  
Morphological Response ◽  
Glucan Synthase ◽  
Content Type ◽  
Safety Issues ◽  
Spontaneous Mutants ◽  
Orally Active

ABSTRACTThe echinocandins are a class of semisynthetic natural products that target β-1,3-glucan synthase (GS). Their proven clinical efficacy combined with minimal safety issues has made the echinocandins an important asset in the management of fungal infection in a variety of patient populations. However, the echinocandins are delivered only parenterally. A screen for antifungal bioactivities combined with mechanism-of-action studies identified a class of piperazinyl-pyridazinones that target GS. The compounds exhibitedin vitroactivity comparable, and in some cases superior, to that of the echinocandins. The compounds inhibit GSin vitro, and there was a strong correlation between enzyme inhibition andin vitroantifungal activity. In addition, like the echinocandins, the compounds caused a leakage of cytoplasmic contents from yeast and produced a morphological response in molds characteristic of GS inhibitors. Spontaneous mutants ofSaccharomyces cerevisiaewith reduced susceptibility to the piperazinyl-pyridazinones had substitutions inFKS1. The sites of these substitutions were distinct from those conferring resistance to echinocandins; likewise, echinocandin-resistant isolates remained susceptible to the test compounds. Finally, we present efficacy and pharmacokinetic data on an example of the piperazinyl-pyridazinone compounds that demonstrated efficacy in a murine model ofCandida glabratainfection.

The mechanism and effect of chronic electrical stimulation of the globus pallidus for treatment of Parkinson disease

2004 ◽  
Vol 100 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
Mitsuhiro Ogura ◽  
Naoyuki Nakao ◽  
Ekini Nakai ◽  
Yuji Uematsu ◽  
Toru Itakura
Keyword(s):  
Electrical Stimulation ◽  
Parkinson Disease ◽  
Globus Pallidus ◽  
Rating Scale ◽  
Underlying Mechanism ◽  
Clinical Effects ◽  
Content Type ◽  
Chronic Electrical Stimulation ◽  
Fine Print ◽  
Stimulation Of

Object. Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. Methods. Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as γ-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. Conclusions. Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.

Effect of stimulation of the medullary reticular formation on cerebral vasomotor tonus and intracranial pressure

1987 ◽  
Vol 66 (4) ◽  
pp. 548-554 ◽  
Author(s):  
Seigo Nagao ◽  
Tsukasa Nishiura ◽  
Hideyuki Kuyama ◽  
Masakazu Suga ◽  
Takenobu Murota
Keyword(s):  
Intracranial Pressure ◽  
Reticular Formation ◽  
Cerebral Blood Volume ◽  
Systemic Arterial Pressure ◽  
Brain Swelling ◽  
Dorsomedial Nucleus ◽  
Medullary Reticular Formation ◽  
Content Type ◽  
Fine Print ◽  
Stimulation Of

✓ The authors report the results of a study to evaluate the effect of stimulation of the medullary reticular formation on cerebral vasomotor tonus and intracranial pressure (ICP) after the hypothalamic dorsomedial nucleus and midbrain reticular formation were destroyed. Systemic arterial pressure (BP), ICP, and local cerebral blood volume (CBV) were continuously recorded in 32 cats. To assess the changes in the cerebral vasomotor tonus, the vasomotor index defined by the increase in ICP per unit change in BP was calculated. In 29 of the 32 animals, BP, ICP, and CBV increased simultaneously immediately after stimulation. The increase in ICP was not secondary to the increase in BP, because the vasomotor index during stimulation was significantly higher than the vasomotor index after administration of angiotensin II. The vasomotor index was high during stimulation of the area around the nucleus reticularis parvocellularis. In animals with the spinal cord transected at the C-2 vertebral level, ICP increased without a change in BP. These findings indicate that the areas stimulated in the medullary reticular formation play an important role in decreasing cerebral vasomotor tonus. This effect was not influenced by bilateral superior cervical ganglionectomy, indicating that there is an intrinsic neural pathway that regulates cerebral vasomotor tonus directly. In three animals, marked biphasic or progressive increases in ICP up to 100 mm Hg were evoked by stimulation. The reduction of cerebral vasomotor tonus and concomitant vasopressor response induced by stimulation of the medullary reticular formation may be one of the causes of acute brain swelling.

Possible necessity for deep brain stimulation of both the ventralis intermedius and subthalamic nuclei to resolve Holmes tremor

2003 ◽  
Vol 99 (3) ◽  
pp. 566-571 ◽  
Author(s):  
Pantaleo Romanelli ◽  
Helen Bronté-Stewart ◽  
Tracy Courtney ◽  
Gary Heit
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Clinical Observation ◽  
Intention Tremor ◽  
Content Type ◽  
Resting Tremor ◽  
Holmes Tremor ◽  
Tremor Analysis ◽  
Deep Brain ◽  
Stimulation Of

✓ Holmes tremor is characterized by resting, postural, and intention tremor. Deep brain stimulation (DBS) of both the nucleus ventralis intermedius (Vim) and the subthalamic nucleus (STN) may be required to control these three tremor components. A 79-year-old man presented with a long-standing combination of resting, postural, and intention tremor, which was associated with severe disability and was resistant to medical treatment. Neuroimaging studies failed to reveal areas of discrete brain damage. A DBS device was placed in the Vim and produced an improvement in both the intention and postural tremor, but there was residual resting tremor, as demonstrated by clinical observation and quantitative tremor analysis. Placement of an additional DBS device in the STN resolved the resting tremor. Stimulation of the Vim or STN alone failed to produce global resolution of mixed tremor, whereas combined Vim—STN stimulation produced global relief without creating noticeable side effects. Combined Vim—STN stimulation can thus be a safe and effective treatment for Holmes tremor.

Transcorneal stimulation of trigeminal nerve afferents to increase cerebral blood flow in rats with cerebral vasospasm: a noninvasive method to activate the trigeminovascular reflex

2002 ◽  
Vol 97 (5) ◽  
pp. 1179-1183 ◽  
Author(s):  
Basar Atalay ◽  
Hayrunnisa Bolay ◽  
Turgay Dalkara ◽  
Figen Soylemezoglu ◽  
Kamil Oge ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Vasospasm ◽  
Trigeminal Nerve ◽  
Nerve Endings ◽  
Noninvasive Method ◽  
Direct Stimulation ◽  
Content Type ◽  
Fine Print ◽  
Stimulation Of

Object. The goal of this study was to investigate whether stimulation of trigeminal afferents in the cornea could enhance cerebral blood flow (CBF) in rats after they have been subjected to experimental subarachnoid hemorrhage (SAH). Cerebral vasospasm following SAH may compromise CBF and increase the risks of morbidity and mortality. Currently, there is no effective treatment for SAH-induced vasospasm. Direct stimulation of the trigeminal nerve has been shown to dilate constricted cerebral arteries after SAH; however, a noninvasive method to activate this nerve would be preferable for human applications. The authors hypothesized that stimulation of free nerve endings of trigeminal sensory fibers in the face might be as effective as direct stimulation of the trigeminal nerve. Methods. Autologous blood obtained from the tail artery was injected into the cisterna magna of 10 rats. Forty-eight and 96 hours later (five rats each) trigeminal afferents were stimulated selectively by applying transcorneal biphasic pulses (1 msec, 3 mA, and 30 Hz), and CBF enhancements were detected using laser Doppler flowmetry in the territory of the middle cerebral artery. Stimulation-induced changes in cerebrovascular parameters were compared with similar parameters in sham-operated controls (six rats). Development of vasospasm was histologically verified in every rat with SAH. Corneal stimulation caused an increase in CBF and blood pressure and a net decrease in cerebrovascular resistance. There were no significant differences between groups for these changes. Conclusions. Data from the present study demonstrate that transcorneal stimulation of trigeminal nerve endings induces vasodilation and a robust increase in CBF. The vasodilatory response of cerebral vessels to trigeminal activation is retained after SAH-induced vasospasm.

scholarly journals Cell Wall-Related Bionumbers and Bioestimates of Saccharomyces cerevisiae and Candida albicans

2013 ◽  
Vol 13 (1) ◽  
pp. 2-9 ◽  
Author(s):  
Frans M. Klis ◽  
Chris G. de Koster ◽  
Stanley Brul
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Candida Albicans ◽  
Cell Size ◽  
Pathogenic Fungus ◽  
Turgor Pressure ◽  
Hyphal Growth ◽  
Biological Research ◽  
Content Type ◽  
Starting Point

ABSTRACTBionumbers and bioestimates are valuable tools in biological research. Here we focus on cell wall-related bionumbers and bioestimates of the budding yeastSaccharomyces cerevisiaeand the polymorphic, pathogenic fungusCandida albicans. We discuss the linear relationship between cell size and cell ploidy, the correlation between cell size and specific growth rate, the effect of turgor pressure on cell size, and the reason why using fixed cells for measuring cellular dimensions can result in serious underestimation ofin vivovalues. We further consider the evidence that individual buds and hyphae grow linearly and that exponential growth of the population results from regular formation of new daughter cells and regular hyphal branching. Our calculations show that hyphal growth allowsC. albicansto cover much larger distances per unit of time than the yeast mode of growth and that this is accompanied by strongly increased surface expansion rates. We therefore predict that the transcript levels of genes involved in wall formation increase during hyphal growth. Interestingly, wall proteins and polysaccharides seem barely, if at all, subject to turnover and replacement. A general lesson is how strongly most bionumbers and bioestimates depend on environmental conditions and genetic background, thus reemphasizing the importance of well-defined and carefully chosen culture conditions and experimental approaches. Finally, we propose that the numbers and estimates described here offer a solid starting point for similar studies of other cell compartments and other yeast species.

Sign in / Sign up

Export Citation Format

Share Document