scholarly journals A 5’ UTR G-quadruplex controls localisation and translation of a potassium leak channel mRNA

2019 ◽  
Author(s):  
Connor J. Maltby ◽  
James P. R. Schofield ◽  
Steven D. Houghton ◽  
Ita O’Kelly ◽  
Mariana Vargas-Caballero ◽  
...  
Keyword(s):  
Cellular Function ◽  
Membrane Potentials ◽  
Hek293 Cells ◽  
Neuronal Dysfunction ◽  
Leak Channel ◽  
G Quadruplex ◽  
Pore Domain ◽  
Normal Cellular Function ◽  
Synaptic Remodelling ◽  
Local Expression

ABSTRACTRNA G-quadruplexes (G4s) are non-canonical secondary structures that have been proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within 3’ UTRs of some neuronal mRNAs are known to control their distal localisation and local translation, contributing to the distinct local proteomes that facilitate the synaptic remodelling attributed to normal cellular function. In this study, we characterise the G4 formation of a (GGN)13 repeat found within the 5’ UTR of KCNK9 mRNA, encoding the potassium 2-pore domain leak channel Task3. Using circular dichroism, we show that this (GGN)13 repeat forms a parallel G4 that exhibits the stereotypical potassium specificity of a G4, remaining thermostable under physiological ionic conditions. The G4 is inhibitory to translation of Task3, which can be overcome through the activity of the G4-specific helicase DHX36, consequently increasing K+ leak currents and decreasing resting membrane potentials in HEK293 cells. Additionally, we observe that this G4 is fundamental to ensuring the delivery of Task3 mRNA to distal primary cortical neurites. It has previously been shown that abnormal Task3 expression correlates with neuronal dysfunction, we therefore posit that this G4 is required for regulated local expression of Task3 leak channels that maintain K+ leak currents within neurons.

scholarly journals A 5′ UTR GGN repeat controls localisation and translation of a potassium leak channel mRNA through G-quadruplex formation

2020 ◽  
Vol 48 (17) ◽  
pp. 9822-9839
Author(s):  
Connor J Maltby ◽  
James P R Schofield ◽  
Steven D Houghton ◽  
Ita O’Kelly ◽  
Mariana Vargas-Caballero ◽  
...  
Keyword(s):  
Hek293 Cells ◽  
Leak Channel ◽  
G Quadruplex ◽  
Rna Immunoprecipitation ◽  
Quadruplex Formation ◽  
Pore Domain ◽  
Normal Cellular Function ◽  
Synaptic Remodelling

Abstract RNA G-quadruplexes (G4s) are secondary structures proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within some neuronal mRNAs are known to control distal localisation and local translation, contributing to distinct local proteomes that facilitate the synaptic remodelling attributed to normal cellular function. In this study, we characterise the G4 formation of a (GGN)13 repeat found within the 5′ UTR of the potassium 2-pore domain leak channel Task3 mRNA. Biophysical analyses show that this (GGN)13 repeat forms a parallel G4 in vitro exhibiting the stereotypical potassium specificity of G4s, remaining thermostable under physiological ionic conditions. Through mouse brain tissue G4-RNA immunoprecipitation, we further confirm that Task3 mRNA forms a G4 structure in vivo. The G4 is inhibitory to translation of Task3 in vitro and is overcome through activity of a G4-specific helicase DHX36, increasing K+ leak currents and membrane hyperpolarisation in HEK293 cells. Further, we observe that this G4 is fundamental to ensuring delivery of Task3 mRNA to distal primary cortical neurites. It has been shown that aberrant Task3 expression correlates with neuronal dysfunction, we therefore posit that this G4 is important in regulated local expression of Task3 leak channels that maintain K+ leak within neurons.

Oxidative stress and cardiovascular health: therapeutic potential of polyphenols

2013 ◽  
Vol 91 (3) ◽  
pp. 198-212 ◽  
Author(s):  
Sandhya Khurana ◽  
Matthew Piche ◽  
Amanda Hollingsworth ◽  
Krishnan Venkataraman ◽  
T.C. Tai
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Recent Progress ◽  
Cardiovascular Health ◽  
Therapeutic Potential ◽  
Cellular Function ◽  
Oxygen Species ◽  
The Impact ◽  
Detrimental Impact ◽  
Normal Cellular Function

Reactive oxygen species (ROS) are important in normal cellular function and physiology. However, oxidative stress resulting from an accumulation of ROS has a detrimental impact on cellular function, and ROS has been implicated in the pathogenesis of a number of diseases, including cardiovascular diseases. This review provides a summary of the impact of ROS on cardiovascular health and diseases, highlighting the therapeutic use of antioxidants. In addition, this review summarizes the health benefits of polyphenols, and the recent progress on understanding the cellular and physiological actions by which polyphenols may impart their beneficial properties on cardiovascular health.

scholarly journals Implications of the mitochondrial interactome of mammalian thioredoxin 2 for normal cellular function and disease

2019 ◽  
Vol 137 ◽  
pp. 59-73 ◽  
Author(s):  
Christos T. Chasapis ◽  
Manousos Makridakis ◽  
Anastassios E. Damdimopoulos ◽  
Jerome Zoidakis ◽  
Vasiliki Lygirou ◽  
...  
Keyword(s):  
Cellular Function ◽  
Thioredoxin 2 ◽  
Normal Cellular Function

Modulation of Ca2+ influx by a mediator released from human tracheal epithelial cells exposed to ozone in vitro

1995 ◽  
Vol 268 (4) ◽  
pp. L558-L564 ◽  
Author(s):  
Q. S. Qu ◽  
L. C. Chen
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Health Effects ◽  
Cellular Function ◽  
Vital Role ◽  
Tracheal Epithelial Cells ◽  
Cell Lysate ◽  
Tracheal Epithelial ◽  
Normal Cellular Function

Intracellular free Ca2+ ([Ca2+]i) plays a vital role both in maintaining normal cellular function and in cell killing. Few studies have been published regarding its role in ozone (O3)-induced health effects. This study investigated the effect and mechanism of O3 exposure on [Ca2+]i in human tracheal epithelial (HTE) cells. HTE cells grown on Costar Transwell inserts with a liquid-gas interface were exposed to 0, 0.05, 0.1, 0.2 and 0.4 ppm O3 at 37 degrees C for 1 h. After exposure, [Ca2+]i was measured using the fluorescent dye Fluo 3. O3 at 0.4 ppm produced a significant increase in [Ca2+]i, and the increases in [Ca2+]i were blocked by verapamil and 8-(diethylamino)-octyl-3,4,5,-trimethoxybenzoate (TMB-8). These results suggest that the O3-induced [Ca2+]i elevation may involve both Ca2+ release from internal stores and Ca2+ influx across the plasma membrane. Furthermore, both buffer and cell lysate of HTE cells exposed to 0.4 ppm O3 caused a rapid increase in [Ca2+]i of THP-1 human phagocytic monocytes, but the buffer and lysate from air exposed cells did not. These results suggest that O3 exposure causes HTE cells to release a diffusible mediator from the empty Ca(2+)-storing organelle and may be responsible for the sustained and persistent [Ca2+]i elevation in HTE cells exposed to 0.4 ppm O3.

Inhibitory action of serum from a Laron dwarf on normal cellular function

1983 ◽  
Vol 39 (6) ◽  
pp. 606-608 ◽  
Author(s):  
B. F. Roth-Schechter ◽  
J. M. Bonardi ◽  
J. G. Juif
Keyword(s):  
Inhibitory Action ◽  
Cellular Function ◽  
Normal Cellular Function

scholarly journals Retrotranslocation: Endoplasmic Reticulum’s Junk Disposal Mechanism

2016 ◽  
Vol 21 (1) ◽  
pp. 9
Author(s):  
Partha Ray
Keyword(s):  
Endoplasmic Reticulum ◽  
Primary Structure ◽  
Quaternary Structure ◽  
Current Knowledge ◽  
Cellular Function ◽  
Misfolded Proteins ◽  
3 Dimensional ◽  
Normal Cellular Function

The primary structure of polypeptides is converted to their final tertiary and quaternary structure by sequential maturation steps, and the endoplasmic reticulum (ER) provides the environment for the polypeptides to attain their proper 3-dimensional architecture. Proteins that misfold or fail to oligomerize with their partners (Chen et al., 1998; Wileman et al., 1990) are quickly degraded, as unfolded or unassembled proteins could interfere with normal cellular function. Retrotranslocation is the process by which terminally misfolded or unassembled ER proteins are translocated back into the cytosol for degradation mediated by the proteasomal machinery. Increasing amounts of evidence now support the fact that the same translocon pore that is involved in the translocation of polypeptides into the ER is also used for the retrotranslocation process. But questions, like how the misfolded proteins are recognized and targeted to the translocon pore, whether the process requires energy, and what pulls the polypeptides as they emerge out of the pore into the cytoplasm, remain to be elucidated. This review addresses our current knowledge about the retrotranslocation process. 

mRNA-specific regulation of translation by poly(A)-binding proteins

2010 ◽  
Vol 38 (6) ◽  
pp. 1517-1522 ◽  
Author(s):  
Hannah M. Burgess ◽  
Nicola K. Gray
Keyword(s):  
Gene Expression ◽  
Translational Control ◽  
Binding Proteins ◽  
Cellular Function ◽  
Translation Factor ◽  
Regulation Of Translation ◽  
Specific Mrnas ◽  
Specific Regulation ◽  
Normal Cellular Function ◽  
Global Translation

The regulation of translation has emerged as a major determinant of gene expression and is critical for both normal cellular function and the development of disease. Numerous studies have highlighted the diverse, and sometimes related, mechanisms which underlie the regulation of global translation rates and the translational control of specific mRNAs. In the present paper, we discuss the emerging roles of the basal translation factor PABP [poly(A)-binding protein] in mRNA-specific translational control in metazoa which suggest that PABP function is more complex than first recognized.

scholarly journals Point-localized and site-specific membrane potential optical recording by engineered single fluorescent nanodiscs

2021 ◽  
Author(s):  
Asaf Grupi ◽  
Zehavit Shapira ◽  
Nurit Degani-Katzav ◽  
Shimon Yudovich ◽  
Shimon Weiss
Keyword(s):  
Membrane Potential ◽  
Cortical Neuron ◽  
Membrane Potentials ◽  
Optical Recording ◽  
Hek293 Cells ◽  
Primary Cortical Neuron ◽  
Voltage Sensing ◽  
Site Specific ◽  
Gaba A ◽  
Specific Membrane

AbstractNanodisc technology was implemented as a platform for voltage nanosensors. A FRET-based voltage sensing scheme employing fluorescent nanodiscs and the hydrophobic ion dipicrylamine (DPA) was developed and utilized to optically record membrane potentials on the single nanodisc level. Ensemble- and single- nanosensor recordings were demonstrated for HEK293 cells and primary cortical neuron cells. Conjugation of nanodiscs to anti-GABA-A antibodies allowed for site specific membrane potential measurements from post synaptic sites.

Protein Folding: From Normal Cellular Function to Pathophysiology

2015 ◽  
pp. 89-103
Author(s):  
Mahmood Rasool ◽  
Arif Malik ◽  
Abdul Manan ◽  
Misbah Sultana ◽  
Mahmood Husain Qazi ◽  
...  
Keyword(s):  
Protein Folding ◽  
Cellular Function ◽  
Normal Cellular Function
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