Acetylation of cytidine residues boosts HIV-1 gene expression by increasing viral RNA stability

Tsai, Kevin; Vasudevan, Ananda Ayyappan Jaguva; MartÍnez-Campos, Cecilia; Emery, Ann; Swanstrom, Ronald; Cullen, Bryan R.

doi:10.1101/2020.01.31.925578

Cited by 5 publications

(3 citation statements)

References 41 publications

(85 reference statements)

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“…In addition to its involvement in cellular processes, the RNA modification has been shown to impact the regulation of the viral life cycle. There is substantial evidence that modifications other than m 6 A can affect the replication of various viruses such as 5methylcytidine (m 5 C) [128], N4-acetylcytidine (ac 4 C) [129], and 2 ′ O-methylation of the ribose fragment of all four ribonucleosides (Nm), etc. [130].…”

Section: The Role Of the M 6 A Modifications In The Genetic Materials...mentioning

confidence: 99%

m6A Methylation in Regulation of Antiviral Innate Immunity

Karandashov,

Kachanov,

Dukich

et al. 2024

Viruses

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The epitranscriptomic modification m6A is a prevalent RNA modification that plays a crucial role in the regulation of various aspects of RNA metabolism. It has been found to be involved in a wide range of physiological processes and disease states. Of particular interest is the role of m6A machinery and modifications in viral infections, serving as an evolutionary marker for distinguishing between self and non-self entities. In this review article, we present a comprehensive overview of the epitranscriptomic modification m6A and its implications for the interplay between viruses and their host, focusing on immune responses and viral replication. We outline future research directions that highlight the role of m6A in viral nucleic acid recognition, initiation of antiviral immune responses, and modulation of antiviral signaling pathways. Additionally, we discuss the potential of m6A as a prognostic biomarker and a target for therapeutic interventions in viral infections.

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Section: The Role Of the M 6 A Modifications In The Genetic Materials...mentioning

confidence: 99%

m6A Methylation in Regulation of Antiviral Innate Immunity

Karandashov,

Kachanov,

Dukich

et al. 2024

Viruses

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“…HIV-1 also uses NAT10 to boost viral gene expression. NAT10 depletion results in the loss of Ac4C from viral transcripts, reducing viral RNA stability and preventing HIV-1 reproduction [81]. Therefore, DNMT2 and NAT10 are potential targets for the development of antiviral drugs.…”

Section: Rna Modification and Viral Infectionmentioning

confidence: 99%

RNA Modification Related Diseases and Sensing Methods

Ohkawa

Konno

2023

Applied Sciences

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Epitranscriptomics is the study of RNA base modifications, including functionally relevant transcriptomic changes. Epitranscriptomics has been actively studied in recent years and has been reported to play important roles in development, homeostasis, the immune system, and various life phenomena such as cancer, neurological diseases, and infectious diseases. However, a major problem is the development of sequencing methods to map RNA base modifications throughout the transcriptome. In recent years, various methods for RNA base modification have been actively studied, and we are beginning to successfully measure base modifications that have been difficult to measure in previous years. In this review, we will discuss in detail the biological significance of RNA modifications and the latest techniques for detecting RNA modifications.

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“…While useful in identifying chemical modification sites without prior knowledge, shortread data are complicated by potential biases introduced during antibody-mediated target RNA enrichment and cDNA preparation [6,7]. Due to the lack of nucleotide-resolution mapping of site-specific modifications, our understanding of chemical modifications is mostly based on cellular perturbation (overexpression or knockout/knockdown) of host effectors [6,[8][9][10][11][12][13][14][15], overlooking the site-specific roles of the epitranscriptome [2,[16][17][18][19][20][21]. These studies often reported disparate effects of epitranscriptome depending on gene type, cellular status and viral species [1,9,22].…”

Section: Introductionmentioning

confidence: 99%

Mapping m6A Sites on HIV-1 RNA Using Oligonucleotide LC-MS/MS

Baek,

Rayhan,

Lee

et al. 2024

MPs

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The biological significance of chemical modifications to the ribonucleic acid (RNA) of human immunodeficiency virus type-1 (HIV-1) has been recognized. However, our understanding of the site-specific and context-dependent roles of these chemical modifications remains limited, primarily due to the absence of nucleotide-resolution mapping of modification sites. In this study, we present a method for achieving nucleotide-resolution mapping of chemical modification sites on HIV-1 RNA using liquid chromatography and tandem mass spectrometry (LC–MS/MS). LC–MS/MS, a powerful tool capable of directly analyzing native RNAs, has proven effective for mapping RNA modifications in small RNA molecules, including ribosomal RNA and transfer RNA. However, longer RNAs have posed challenges, such as the 9 Kb HIV-1 virion RNA, due to the complexity of and ambiguity in mass differences among RNase T1-cleaved RNA fragments in LC-MS/MS data. Here, we introduce a new target RNA enrichment method to isolate small local RNA fragments of HIV-1 RNA that potentially harbor site-specific N6-methyladenosine (m6A) modifications. In our initial trial, we used target-specific DNA probes only and encountered insufficient RNA fragmentation due to inefficient S1 digestion near the target site. Recognizing that inefficient S1 digestion by HIV-1 RNA is likely due to the formation of secondary structures in proximity to the target site, we designed multiple DNA probes annealing to various sites of HIV-1 RNA to better control the structures of RNA substrates for S1 digestion. The use of these non-target DNA probes significantly improved the isolation of more homogeneous target RNA fragments of approximately 50 bases in length. Oligonucleotide LC-MS/MS analysis of these isolated target RNA fragments successfully separated and detected both m6A-methylated and non-methylated oligomers at the two m6A-predicted sites. The principle of this new target enrichment strategy holds promise and should be broadly applicable to the analysis of any lengthy RNA that was previously deemed infeasible for investigation using oligonucleotide LC-MS/MS.

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Acetylation of cytidine residues boosts HIV-1 gene expression by increasing viral RNA stability

Cited by 5 publications

References 41 publications

m6A Methylation in Regulation of Antiviral Innate Immunity

m6A Methylation in Regulation of Antiviral Innate Immunity

RNA Modification Related Diseases and Sensing Methods

Mapping m6A Sites on HIV-1 RNA Using Oligonucleotide LC-MS/MS

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