The Effects of Ultraviolet Radiation on Nucleoside Modifications in RNA

Sun, Congliang; Jora, Manasses; Solivio, Beulah; Limbach, Patrick A.; Addepalli, Balasubrahmanyam

doi:10.1021/acschembio.7b00898

Cited by 19 publications

(33 citation statements)

References 35 publications

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“…However, the authors also pointed out that abasic sites and unknown oxidation products of modified tRNA Gly nucleotides might have escaped their analysis. Another study, using UV-induced oxidative stress, did describe degradation of many post-transcriptional modifications under oxidative stress conditions ( Sun et al, 2018 ).…”

Section: The Transcribed Mrna Is Translated To Proteinsmentioning

confidence: 99%

Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology

Fasnacht

Polacek

2021

Front. Mol. Biosci.

127

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Ever since the “great oxidation event,” Earth’s cellular life forms had to cope with the danger of reactive oxygen species (ROS) affecting the integrity of biomolecules and hampering cellular metabolism circuits. Consequently, increasing ROS levels in the biosphere represented growing stress levels and thus shaped the evolution of species. Whether the ROS were produced endogenously or exogenously, different systems evolved to remove the ROS and repair the damage they inflicted. If ROS outweigh the cell’s capacity to remove the threat, we speak of oxidative stress. The injuries through oxidative stress in cells are diverse. This article reviews the damage oxidative stress imposes on the different steps of the central dogma of molecular biology in bacteria, focusing in particular on the RNA machines involved in transcription and translation.

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Section: The Transcribed Mrna Is Translated To Proteinsmentioning

confidence: 99%

Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology

Fasnacht

Polacek

2021

Front. Mol. Biosci.

127

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“…Two important and active areas of research include the characterization of post-transcriptional modifications to ribonucleic acid (RNA) [3] and the development of synthetic antisense and aptamer-based nucleic acids for gene silencing experiments and therapeutics [4,5]. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been the primary technique for the direct detection of unmodified and modified oligonucleotides with various applications including the characterization of endogenous modifications [6,7], xenobiotic modifications [8], and synthetic modifications [9,10] of the base, ribose, or phosphodiester backbone.…”

Section: Introductionmentioning

confidence: 99%

Oligonucleotide analysis by hydrophilic interaction liquid chromatography-mass spectrometry in the absence of ion-pair reagents

Lobue

Jora

Addepalli

et al. 2019

Journal of Chromatography A

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Improving our understanding of nucleic acids, both in biological and synthetic applications, remains a bustling area of research for both academic and industrial laboratories. As nucleic acids research evolves, so must the analytical techniques used to characterize nucleic acids. One powerful analytical technique has been coupled liquid chromatography-tandem mass spectrometry (LC-MS/MS). To date, the most successful chromatographic mode has been ionpairing reversed-phase liquid chromatography. Hydrophilic interaction liquid chromatography (HILIC), in the absence of ion-pair reagents, has been investigated here as an alternative chromatographic approach to the analysis of oligonucleotides. By combining a mobile phase system using commonly employed in liquid chromatography-mass spectrometry (LC-MS)-i.e., water, acetonitrile, and ammonium acetate-and a new, commercially available diol-based HILIC column, high chromatographic and mass spectrometric performance for a wide range of oligonucleotides is demonstrated. Particular applications of HILIC-MS for the analysis of deoxynucleic acid (DNA) oligomers, modified and unmodified oligoribonucleotides, and phosphorothioate DNA oligonucleotides are presented. Based on the LC-MS performance, this HILIC-based approach provides an attractive, sensitive and robust alternative to prior ion-pairing dependent methods with potential utility for both qualitative and quantitative analyses of oligonucleotides without compromising chromatographic or mass spectrometric performance.

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“…The wobble modification in tRNA, mnm 5 s 2 U, is susceptible to UVA-induced oxidative degradation and the Δ trmU strain of E. coli deficient in this modification exhibited elevated levels of oxidized guanosine in tRNA upon exposure to UVA ( Sun et al, 2018 ). We tested the possibility of such behavior under Fenton-reaction induced oxidative stress conditions.…”

Section: Resultsmentioning

confidence: 99%

“…The naturally occurring PTMs impart structural stability ( Decatur and Fournier, 2002 ; Väre et al, 2017 ), facilitate interactions between ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA) and translation factors ( Polikanov et al, 2015 ), and impart translation efficiency ( Agris et al, 2017 ). Our laboratory has previously documented oxidative changes to ribonucleosides and their PTMs in E. coli upon UVA-induced oxidative stress ( Sun et al, 2018 ) and these oxidative changes seem to localize at specific regions of tRNA ( Barciszewski et al, 1999 ; Sun et al, 2020 ). Here, we show that the oxidative changes in RNA are altered by the bound proteins and post-transcriptional nucleoside modifications such as methylations or the hypermodification, 5-methylaminomethyl-2-thiouridine (mnm 5 s 2 U), found in ribosomal RNA and tRNA, respectively, of an E. coli model system.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Damage to RNA is Altered by the Presence of Interacting Proteins or Modified Nucleosides

Estevez

Valesyan

Jora

et al. 2021

Front. Mol. Biosci.

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Oxidative stress triggered by the Fenton reaction (chemical) or UVR exposure (photo) can damage cellular biomolecules including RNA through oxidation of nucleotides. Besides such xenobiotic chemical modifications, RNA also contains several post-transcriptional nucleoside modifications that are installed by enzymes to modulate structure, RNA-protein interactions, and biochemical functions. We examined the extent of oxidative damage to naturally modified RNA which is required for cellular protein synthesis under two different contexts. The extent of oxidative damage is higher when RNA is not associated with proteins, but the degree of damage is lower when the RNA is presented in the form of a ribonucleoprotein complex, such as an intact ribosome. Our studies also indicate that absence of methylations in ribosomal RNA at specific positions could make it more susceptible to photooxidative stress. However, the extent of guanosine oxidation varied with the position at which the modification is deficient, indicating position-dependent structural effects. Further, an E. coli strain deficient in 5-methylaminomethyl-2-thiouridine (mnm5s2U) (found in lysine and glutamate tRNA anticodon) is more vulnerable to oxidative RNA damage compared to its wildtype strain suggesting an auxiliary function for the mnm5s2U modification. These studies indicate that oxidative damage to RNA is altered by the presence of enzymatic modified nucleosides or protein association inside the cell.

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The Effects of Ultraviolet Radiation on Nucleoside Modifications in RNA

Cited by 19 publications

References 35 publications

Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology

Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology

Oligonucleotide analysis by hydrophilic interaction liquid chromatography-mass spectrometry in the absence of ion-pair reagents

Oxidative Damage to RNA is Altered by the Presence of Interacting Proteins or Modified Nucleosides

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