Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability

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

doi:10.1016/j.chom.2020.05.011

Cited by 116 publications

(95 citation statements)

References 42 publications

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“…Our analyses showed that CpG islands were located at the beginnings of ORFs, thus pointing to their essential regulatory roles in the SARS-CoV-2 lifecycle. On the other hand, CpG islands in RNA are very often targets of methylation enzymes and it has been demonstrated that viral genome’s methylation could lead to the inhibition of both DNA and RNA viruses [ 44 , 45 ]. Interestingly, there is correlation between folate-related enzyme mutation [methylenetetrahydrofolate reductase (MTHFR)] and the COVID-19 disease’s severity.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

Goswami

Bartas

Lexa

et al. 2020

Briefings in Bioinformatics

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SARS-CoV-2 is an intensively investigated virus from the order Nidovirales ( Coronaviridae family) that causes COVID-19 disease in humans. Through enormous scientific effort, thousands of viral strains have been sequenced to date, thereby creating a strong background for deep bioinformatics studies of the SARS-CoV-2 genome. In this study, we inspected high-frequency mutations of SARS-CoV-2 and carried out systematic analyses of their overlay with inverted repeat (IR) loci and CpG islands. The main conclusion of our study is that SARS-CoV-2 hot-spot mutations are significantly enriched within both IRs and CpG island loci. This points to their role in genomic instability and may predict further mutational drive of the SARS-CoV-2 genome. Moreover, CpG islands are strongly enriched upstream from viral ORFs and thus could play important roles in transcription and the viral life cycle. We hypothesize that hypermethylation of these loci will decrease the transcription of viral ORFs and could therefore limit the progression of the disease.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

Goswami

Bartas

Lexa

et al. 2020

Briefings in Bioinformatics

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“…This may relate to the fact that ac 4 C can form more stable base pairs with guanosine residues 105 . Recently, we reported the mapping of ac 4 C residues in HIV-1 transcripts (Box 2) and reported that the loss of NAT10 expression results in a decline in HIV-1 gene expression in infected T cells 106 . However, unlike m 5 C, ac 4 C was found to increase HIV-1 gene expression by enhancing RNA stability, while viral mRNA translation was unaffected.…”

Section: -Methylcytidinementioning

confidence: 99%

“…In addition, uv-light crosslinking of proteins to 4Su results in a thymidine-to-cytidine conversion during reverse transcription, which allows the removal of all background reads during final data analysis 136 . Antibody-based methods can easily be adapted to mapping different modifications, as we have previously demonstrated by performing PA-m 6 A-seq with m 5 c and ac 4 c antibodies 80,106 , whereas m 6 A-seq has also been adapted to ac 4 c 80,104 . Adapting miclIP to other antibodies would require additional testing to discover the preferred mutation induced by uv-light crosslinking of the specific antibody.…”

Section: Box 2 | Techniques Used To Map Epitranscriptomic Modificationsmentioning

confidence: 99%

Epigenetic and epitranscriptomic regulation of viral replication

2020

Self Cite

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Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. However, viruses have evolved countermeasures that prevent the epigenetic silencing of their genes during lytic replication, and they can also take advantage of epigenetic silencing to establish latent infections. By contrast, the various covalent modifications added to RNAs, termed epitranscriptomic modifications, can positively regulate mRNA translation and/or stability, and both DNA and RNA viruses have evolved to utilize epitranscriptomic modifications as a means to maximize viral gene expression. As a consequence, both chromatin and RNA modifications could serve as novel targets for the development of antivirals. In this Review, we discuss how host epigenetic and epitranscriptomic processes regulate viral gene expression at the levels of chromatin and RNA function, respectively, and explore how viruses modify, avoid or utilize these processes in order to regulate viral gene expression.

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“…These modifications include 2′ O-methylated ribonucleotides (Am, Gm, and Cm), 1-methylguanosine (m 1 G), and 7-methylguanosine (m 7 G). It was recently reported that cytidines of HIV-1 RNAs are acetylated by NAT10, and this modification results in stabilization of viral RNAs [ 224 ]. However, it remains largely unknown as to whether APOBEC3s impact RNA modification patterns on viral gRNA via its binding to gRNA ( Figure 2 ).…”

Section: An Alternative Deaminase-independent Anti-mulv Mechanism mentioning

confidence: 99%

Deaminase-Independent Mode of Antiretroviral Action in Human and Mouse APOBEC3 Proteins

Hakata

Miyazawa

2020

Microorganisms

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Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins (APOBEC3s) are deaminases that convert cytosines to uracils predominantly on a single-stranded DNA, and function as intrinsic restriction factors in the innate immune system to suppress replication of viruses (including retroviruses) and movement of retrotransposons. Enzymatic activity is supposed to be essential for the APOBEC3 antiviral function. However, it is not the only way that APOBEC3s exert their biological function. Since the discovery of human APOBEC3G as a restriction factor for HIV-1, the deaminase-independent mode of action has been observed. At present, it is apparent that both the deaminase-dependent and -independent pathways are tightly involved not only in combating viruses but also in human tumorigenesis. Although the deaminase-dependent pathway has been extensively characterized so far, understanding of the deaminase-independent pathway remains immature. Here, we review existing knowledge regarding the deaminase-independent antiretroviral functions of APOBEC3s and their molecular mechanisms. We also discuss the possible unidentified molecular mechanism for the deaminase-independent antiretroviral function mediated by mouse APOBEC3.

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Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability

Cited by 116 publications

References 42 publications

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

Epigenetic and epitranscriptomic regulation of viral replication

Deaminase-Independent Mode of Antiretroviral Action in Human and Mouse APOBEC3 Proteins

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