Effect of Depurination on Cellular and Viral RNA

Jobst, Kass A.; Klenov, Alexander; Neller, Kira C. M.; Hudak, Katalin A.

doi:10.1007/978-3-319-34175-0_12

Cited by 8 publications

(7 citation statements)

References 104 publications

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“…Recombinant expression of dsRNA-transmembrane channels from Caenorhabditis elegans, the nematode model for RNAi, has also been used to enhance dsRNA uptake in B. mori and D. melanogaster cultured cells (Table S5). Other approaches for overcoming limitations in dsRNA uptake in Pest Manag Sci 2019; 75: [18][19][20][21][22][23][24][25][26][27][28] insects include expressing dsRNA in recombinant microbes for oral delivery to insects (D. suzukii in Table S5), genetically engineering symbiotic bacteria to express and deliver dsRNA intracellularly, 28 or enhancing clathrin-dependent endocytosis using arachidonic acid or hydrogen peroxide, as was done for B. dorsalis (Table S5).…”

Section: Endocytosismentioning

confidence: 99%

“…17 RNA is also vulnerable to depurination at pH < 3.0. 18 The highly alkaline environment of lepidopteran gut is particularly concerning for dsRNA stability, but alkaline conditions in the gut of orthopterans, dipterans, and hymenopterans may also reduce RNAi efficiency by hydrolyzing dsRNA, although this has not been experimentally investigated. Furthermore, dsRNases seem to have the greatest enzymatic activity in alkaline conditions (L. migratoria, Table S2).…”

Section: Physiological Phmentioning

confidence: 99%

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Molecular mechanisms influencing efficiency of RNA interference in insects

Cooper

Silver

Zhang

et al. 2018

Pest Management Science

284

314

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RNA interference (RNAi) is an endogenous, sequence-specific gene-silencing mechanism elicited by small RNA molecules. RNAi is a powerful reverse genetic tool, and is currently being utilized for managing insects and viruses. Widespread implementation of RNAi-based pest management strategies is currently hindered by inefficient and highly variable results when different insect species, strains, developmental stages, tissues, and genes are targeted. Mechanistic studies have shown that double-stranded ribonucleases (dsRNases), endosomal entrapment, deficient function of the core machinery, and inadequate immune stimulation contribute to limited RNAi efficiency. However, a comprehensive understanding of the molecular mechanisms limiting RNAi efficiency remains elusive. Recent advances in dsRNA stability in physiological tissues, dsRNA internalization into cells, the composition and function of the core RNAi machinery, as well as small-interfering RNA/double-stranded RNA amplification and spreading mechanisms are reviewed to establish a global understanding of the obstacles impeding wider understanding of RNAi mechanisms in insects. © 2018 Society of Chemical Industry.

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Section: Endocytosismentioning

confidence: 99%

Section: Physiological Phmentioning

confidence: 99%

Molecular mechanisms influencing efficiency of RNA interference in insects

Cooper

Silver

Zhang

et al. 2018

Pest Management Science

284

314

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“…80 N7 alkylated guanine was shown to depurinate 10 6 more rapidly than guanine under physiological conditions. 81 RNA is considered less prone to depurination, because the 2'-OH destabilizes the oxocarbonium intermediate, 80 but several cases in RNA have been reported, 82 which could hamper interpretation of obtained data. There appears to be a physiological relevance to this reaction and enzymatic repair pathways have been identified.…”

Section: Nitrogen Mustardsmentioning

confidence: 99%

Chemical RNA Crosslinking: Mechanisms, Computational Analysis and Biological Applications

Velema

2022

Preprint

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In recent years, RNA has emerged as a multifaceted biomolecule that is involved in virtually every function of the cell and is critical for human health. This has led to a substantial increase in research efforts to uncover the many chemical and biological aspects of RNA and target RNA for therapeutic purposes. In particular, analysis of RNA structures and interactions in cells has been critical for understanding their diverse functions and druggability. In the last 5 years, several chemical methods have been developed to achieve this goal, using chemical crosslinking combined with high-throughput sequencing and computational analysis. Applications of these methods resulted in important new insights into RNA functions in a variety of biological contexts. Given the rapid development of new chemical technologies, a thorough review on the past and future of this field is provided. In particular, the various RNA crosslinkers and their mechanisms, the computational analysis and challenges and illustrative examples from recent literature are discussed.

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“…However, mis-repairing can occur, which leads to mutation and, in some cases, oncogenesis [ 9 ]. The depurination of RNA, depending on context, has multiple downstream effects such as halting translation [ 10 ], preventing the packaging of viral RNA into capsids [ 11 ], or inhibiting protein synthesis in ribosomes by cleavage of a key catalytic adenine [ 12 ]. Oxford Nanopore Technologies sequencing can potentially capture the entire spectrum of modifications present on nonamplified DNA or RNA.…”

Section: Introductionmentioning

confidence: 99%

RIPpore: A Novel Host-Derived Method for the Identification of Ricin Intoxication through Oxford Nanopore Direct RNA Sequencing

Ryan

Harrison

Trivett

et al. 2022

Toxins

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Ricin is a toxin which enters cells and depurinates an adenine base in the sarcin−ricin loop in the large ribosomal subunit, leading to the inhibition of protein translation and cell death. We postulated that this depurination event could be detected using Oxford Nanopore Technologies (ONT) direct RNA sequencing, detecting a change in charge in the ricin loop. In this study, A549 cells were exposed to ricin for 2–24 h in order to induce depurination. In addition, a novel software tool was developed termed RIPpore that could quantify the adenine modification of ribosomal RNA induced by ricin upon respiratory epithelial cells. We provided demonstrable evidence for the first time that this base change detected is specific to RIP activity using a neutralising antibody against ricin. We believe this represents the first detection of depurination in RNA achieved using ONT sequencers. Collectively, this work highlights the potential for ONT and direct RNA sequencing to detect and quantify depurination events caused by ribosome−inactivating proteins such as ricin. RIPpore could have utility in the evaluation of new treatments and/or in the diagnosis of exposure to ricin.

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Effect of Depurination on Cellular and Viral RNA

Cited by 8 publications

References 104 publications

Molecular mechanisms influencing efficiency of RNA interference in insects

Molecular mechanisms influencing efficiency of RNA interference in insects

Chemical RNA Crosslinking: Mechanisms, Computational Analysis and Biological Applications

RIPpore: A Novel Host-Derived Method for the Identification of Ricin Intoxication through Oxford Nanopore Direct RNA Sequencing

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