scholarly journals Oxidative Modifications of RNA and Its Potential Roles in Biosystem

2021 ◽  
Vol 8 ◽  
Author(s):  
Mikiei Tanaka ◽  
P. Boon Chock
Keyword(s):  
Protein Synthesis ◽  
Elevated Level ◽  
Oxidative Modification ◽  
Cross Linking ◽  
Strand Breaks ◽  
Cellular Effects ◽  
Translational Activity ◽  
Pathological Conditions ◽  
Rna Oxidation ◽  
Translation Errors

Elevated level of oxidized RNA was detected in vulnerable neurons in Alzheimer patients. Subsequently, several diseases and pathological conditions were reported to be associated with RNA oxidation. In addition to several oxidized derivatives, cross-linking and unique strand breaks are generated by RNA oxidation. With a premise that dysfunctional RNA mediated by oxidation is the pathogenetic molecular mechanism, intensive investigations have revealed the mechanism for translation errors, including premature termination, which gives rise to aberrant polypeptides. To this end, we and others revealed that mRNA oxidation could compromise its translational activity and fidelity. Under certain conditions, oxidized RNA can also induce several signaling pathways, to mediate inflammatory response and induce apoptosis. In this review, we focus on the oxidative modification of RNA and its resulting effect on protein synthesis as well as cell signaling. In addition, we will also discuss the potential roles of enzymatic oxidative modification of RNA in mediating cellular effects.

Consequences of RNA oxidation on protein synthesis rate and fidelity: implications for the pathophysiology of neuropsychiatric disorders

2017 ◽  
Vol 45 (5) ◽  
pp. 1053-1066 ◽  
Author(s):  
Akihiko Nunomura ◽  
Hyoung-gon Lee ◽  
Xiongwei Zhu ◽  
George Perry
Keyword(s):  
Protein Synthesis ◽  
Oxidative Damage ◽  
Neuropsychiatric Disorders ◽  
Oxidative Modification ◽  
Mammalian Brain ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Translation System ◽  
Rna Oxidation ◽  
Cyt C

Unlike DNA, oxidative damage to RNA has received little attention presumably due to the assumed transient nature of RNA. However, RNAs including mRNA can persist for several hours to days in certain tissues and are demonstrated to sustain greater oxidative damage than DNA. Because neuronal cells in the brain are continuously exposed to reactive oxygen species due to a high oxygen consumption rate, it is not surprising that neuronal RNA oxidation is observed as a common feature at an early stage in a series of neurodegenerative disorders. A recent study on a well-defined bacterial translation system has revealed that mRNA containing 8-oxo-guanosine (8-oxoGuo) has little effect on fidelity despite the anticipated miscoding. Indeed, 8-oxoGuo-containing mRNA leads to ribosomal stalling with a reduced rate of peptide-bond formation by 3–4 orders of magnitude and is subject to no-go decay, a ribosome-based mRNA surveillance mechanism. Another study demonstrates that transfer RNA oxidation catalyzed by cytochrome c (cyt c) leads to its depurination and cross-linking, which may facilitate cyt c release from mitochondria and subsequently induce apoptosis. Even more importantly, a discovery of oxidized microRNA has been recently reported. The oxidized microRNA causes misrecognizing the target mRNAs and subsequent down-regulation in the protein synthesis. It is noteworthy that oxidative modification to RNA not only interferes with the translational machinery but also with regulatory mechanisms of noncoding RNAs that contribute toward the biological complexity of the mammalian brain. Oxidative RNA damage might be a promising therapeutic target potentially useful for an early intervention of diverse neuropsychiatric disorders.

scholarly journals Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

2021 ◽  
Vol 3 (2) ◽  
pp. 312-341
Author(s):  
Maria Neus Ballester Roig ◽  
Tanya Leduc ◽  
Cassandra C. Areal ◽  
Valérie Mongrain
Keyword(s):  
Sleep Time ◽  
Sleep Regulation ◽  
Neuronal Communication ◽  
Cellular Effects ◽  
Pathological Conditions ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Cellular Pathways ◽  
Phosphoinositide 3 Kinase ◽  
Protein Kinase Akt

Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhynchophylline (Rhy) is one of the principal alkaloids in Uncaria species. Although treatment with Rhy alone has not been tested in humans, observations in rodents show that Rhy increases sleep time. However, the mechanisms by which Rhy could modulate sleep have not been comprehensively described. In this review, we are highlighting cellular pathways that are shown to be targeted by Rhy and which are also known for their implications in the regulation of wakefulness and sleep. We conclude that Rhy can impact sleep through mechanisms involving ion channels, N-methyl-d-aspartate (NMDA) receptors, tyrosine kinase receptors, extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT), and nuclear factor-kappa B (NF-κB) pathways. In modulating multiple cellular responses, Rhy impacts neuronal communication in a way that could have substantial effects on sleep phenotypes. Thus, understanding the mechanisms of action of Rhy will have implications for sleep pharmacology.

scholarly journals Native cross-links in collagen fibrils induce resistance to human synovial collagenase

1979 ◽  
Vol 181 (3) ◽  
pp. 639-645 ◽  
Author(s):  
C A Vater ◽  
E D Harris ◽  
R C Siegel
Keyword(s):  
Lysyl Oxidase ◽  
Collagen Fibrils ◽  
Bone Collagen ◽  
Collagen Molecule ◽  
Cross Linking ◽  
Pathological Conditions ◽  
Insoluble Material ◽  
Induce Resistance ◽  
Cross Links

A model system consisting of highly purified lysyl oxidase and reconstituted lathyritic chick bone collagen fibrils was used to study the effect of collagen cross-linking on collagen degradation by mammalian collagenase. The results indicate that synthesis of approx. 0.1 Schiff-base cross-link per collagen molecule results in a 2–3-fold resistance to human synovial collagenase when compared with un-cross-linked controls or samples incubated in the presence of beta-aminopropionitrile to inhibit cross-linking. These results confirm previous studies utilizing artificially cross-linked collagens, or collagens isolated as insoluble material after cross-linking in vivo, and suggest that increased resistance to collagenase may be one of the earliest effects of cross-linking in vivo. The extent of intermolecular cross-linking among collagen fibrils may provide a mechanism for regulating the rate of collagen catabolism relative to synthesis in normal and pathological conditions.

scholarly journals DNA DAMAGE AND REPAIR IN EUKARYOTIC CELLS

Genetics ◽  
1974 ◽  
Vol 78 (1) ◽  
pp. 139-148
Author(s):  
R B Painter
Keyword(s):  
Ionizing Radiation ◽  
Excision Repair ◽  
Double Strand Breaks ◽  
Single Strand ◽  
Premature Aging ◽  
Cross Linking ◽  
Base Damage ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Post Replication Repair

ABSTRACT Damage in DNA after irradiation can be classified into five kinds: base damage, single-strand breaks, double-strand breaks, DNA-DNA cross-linking, and DNA-protein cross-linking. Of these, repair of base damage is the best understood. In eukaryotes, at least three repair systems are known that can deal with base damage: photoreactivation, excision repair, and post-replication repair. Photoreactivation is specific for UV-induced damage and occurs widely throughout the biosphere, although it seems to be absent from placental mammals. Excision repair is present in prokaryotes and in animals but does not seem to be present in plants. Post-replication repair is poorly understood. Recent reports indicate that growing points in mammalian DNA simply skip past UV-induced lesions, leaving gaps in newly made DNA that are subsequently filled in by de novo synthesis. Evidence that this concept is oversimplified or incorrect is presented.—Single-strand breaks are induced by ionizing radiation but most cells can rapidly repair most or all of them, even after supralethal doses. The chemistry of the fragments formed when breaks are induced by ionizing radiation is complex and poorly understood. Therefore, the intermediate steps in the repair of single-strand breaks are unknown. Double-strand breaks and the two kinds of cross-linking have been studied very little and almost nothing is known about their mechanisms for repair.—The role of mammalian DNA repair in mutations is not known. Although there is evidence that defective repair can lead to cancer and/or premature aging in humans, the relationship between the molecular defects and the diseased state remains obscure.

scholarly journals Composition of the λ plasmid heritable replicationcomplex

2002 ◽  
Vol 364 (3) ◽  
pp. 857-862 ◽  
Author(s):  
Katarzyna POTRYKUS ◽  
Sylwia BARAŃSKA ◽  
Alicja WĘGRZYN ◽  
Grzegorz WĘGRZYN
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Protein Synthesis ◽  
Plasmid Dna ◽  
Pcr Analysis ◽  
Cross Linking ◽  
Bacteriophage Λ ◽  
Yeast Saccharomyces Cerevisiae ◽  
Replication Complex

Previous studies indicated during replication of plasmids derived from bacteriophage λ (the so-called λ plasmids), that, once assembled, replication complex can be inherited by one of the two daughter plasmid copies after each replication round, and may function in subsequent replication rounds. It seems that similar processes occur during replication of other DNA molecules, including chromosomes of the yeast Saccharomyces cerevisiae. However, apart from some suggestions based on genetic experiments, composition of the λ heritable replication complex remains unknown. In amino acid-starved Escherichia coli relA mutants, replication of λ plasmid DNA is carried out exclusively by the heritable replication complex as assembly of new complexes is impaired due to inhibition of protein synthesis. Here, using a procedure based on in vivo cross-linking, cell lysis, immunoprecipitation with specific sera, de-cross-linking and PCR analysis, we demonstrate that the λ heritable replication complex consists of O, P, DnaB and, perhaps surprisingly, DnaK proteins.

scholarly journals LIGAND-INDUCED MOVEMENT OF LYMPHOCYTE MEMBRANE MACROMOLECULES

1973 ◽  
Vol 137 (3) ◽  
pp. 675-689 ◽  
Author(s):  
Emil R. Unanue ◽  
Morris J. Karnovsky ◽  
Howard D. Engers
Keyword(s):  
Protein Synthesis ◽  
Cell Membrane ◽  
Cell Surface ◽  
Oxidative Phosphorylation ◽  
Cross Linking ◽  
Lymphocyte Membrane ◽  
Compact Zone ◽  
Entire Cell ◽  
Freeze Etching ◽  
Spleen Lymphocytes

Spleen lymphocytes were studied for the movement and interiorization of complexes of anti-Ig-surface Ig. The movement of the complex into a small, compact zone of the cell membrane (forming a cap) was inhibited by drugs that inhibited glycolysis and oxidative phosphorylation, but not by drugs that affected protein synthesis. Dead lymphocytes did not form caps. Freeze-etching techniques revealed that inhibited lymphocytes showed formation of multiple small complexes over the entire cell surface. Inhibitors of glycolysis and of oxidative phosphorylation also inhibited the interiorization and catabolism of radioiodinated anti-Ig. We hypothesize that cross-linking of all the surface Ig triggers the membrane movements that are required to pull the lattice into one zone of the cell.

scholarly journals Production of Recombinant Horseradish Peroxidase in an Engineered Cell-free Protein Synthesis System

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Jin Park ◽  
Dong-Myung Kim
Keyword(s):  
Protein Synthesis ◽  
Horseradish Peroxidase ◽  
Aminolevulinic Acid ◽  
Synthesis System ◽  
Prosthetic Group ◽  
Reaction Conditions ◽  
Translational Activity ◽  
A Cell ◽  
Template Dna ◽  
Cell Free Protein Synthesis

One of the main advantages of a cell-free synthesis system is that the synthetic machinery of cells can be modularized and re-assembled for desired purposes. In this study, we attempted to combine the translational activity of Escherichia coli extract with a heme synthesis pathway for the functional production of horseradish peroxidase (HRP). We first optimized the reaction conditions and the sequence of template DNA to enhance protein expression and folding. The reaction mixture was then supplemented with 5-aminolevulinic acid synthase to facilitate co-synthesis of the heme prosthetic group from glucose. Combining the different synthetic modules required for protein synthesis and cofactor generation led to successful production of functional HRP in a cell-free synthesis system.

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