A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA

Qi, Xiaoyu; Yan, Qin; Shang, Yuancui; Zhao, Runran; Ding, Xiangya; Gao, Shou‐Jiang; Wan, Li; Liu, Chun

doi:10.1038/s41418-022-01011-1

Cited by 8 publications

(6 citation statements)

References 75 publications

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“…Our latest study has demonstrated that KSHV reactivation does not affect the expression level of NAT10 protein [14], but the mechanisms underlying NAT10-mediated KSHV reactivation need further explorations. We and others have previously found that lactate accumulates not only during KSHV latent infection [22,23], but also in the medium of iSLK-KSHV cells after doxycycline induction (Fig. 2A), indicating that lactate-driven lysine lactylation may be involved in NAT10-mediated viral reactivation.…”

Section: Nat10 Lactylation At Lys290 Facilitates Kshv Lytic Genes Tra...mentioning

confidence: 63%

Lactylation of NAT10 promotes N4‐acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation

Yan,

Zhou,

et al. 2024

Cell Death Differ

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N4-acetylcytidine (ac4C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac4C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac4C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac4C level of tRNASer-CGA-1-1. Mutagenesis at the ac4C site in tRNASer-CGA-1-1 inhibited its ac4C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNASer-CGA-1-1 ac4C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac4C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.

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Section: Nat10 Lactylation At Lys290 Facilitates Kshv Lytic Genes Tra...mentioning

confidence: 63%

Lactylation of NAT10 promotes N4‐acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation

Yan,

Zhou,

et al. 2024

Cell Death Differ

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“…Studies presenting the expression of this gene in tumor tissues have indicated that it can be both overexpressed and downregulated under the influence of disease [ 27 ]. Nevertheless, the role of KLHL3 in the pathogenesis of cancers formed through viral interaction appears to be well-proven [ 28 ]. Indeed, it appears that KLHL3 protein expression is significantly higher in cells expressing vIRF1 (viral interferon regulatory factor 1), as well as in cells infected with KSHV (Kaposi’s sarcoma-associated herpesvirus).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it appears that KLHL3 protein expression is significantly higher in cells expressing vIRF1 (viral interferon regulatory factor 1), as well as in cells infected with KSHV (Kaposi’s sarcoma-associated herpesvirus). Researchers have found that KLHL3 mediates the infection and replication of KSHV-induced tumorigenesis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol

Wierzbicka,

Semik-Gurgul,

Świątkiewicz

et al. 2023

IJMS

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Maintaining an appropriate concentration of vitamin D is essential for the proper functioning of the body, regardless of age. Nowadays, there are more and more indications that vitamin D supplementation at higher than standard doses may show protective and therapeutic effects. Our study identified differences in the body’s response to long-term supplementation with cholecalciferol at an increased dose. Two groups of pigs were used in the experiment. The first group received a standard dose of cholecalciferol (grower, 2000 IU/kg feed, and finisher, 1500 IU/kg feed), and the second group received an increased dose (grower, 3000 IU/kg feed, and finisher, 2500 IU/kg feed). After slaughter, lung samples were collected and used for RRBS and mRNA sequencing. Analysis of the methylation results showed that 2349 CpG sites had significantly altered methylation patterns and 1116 (47.51%) identified DMSs (Differentially Methylated Sites) were related to genes and their regulatory sites. The mRNA sequencing results showed a significant change in the expression of 195 genes. The integrated analysis identified eleven genes with DNA methylation and mRNA expression differences between the analyzed groups. The results of this study suggested that an increased vitamin D intake may be helpful for the prevention of lung cancer and pulmonary fibrosis. These actions may stem from the influence of vitamin D on the expression of genes associated with collagen production, such as SHMT1, UGT1A6, and ITIH2.The anti-cancer properties of vitamin D are also supported by changes in KLHL3 and TTPA gene expression.

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“…In addition to utilizing the host UPS to facilitate viral entry, enhance infected cell proliferation/survival, promote lytic onset, and evade immune processes, KSHV conducts a complete reprogramming of host cell metabolism. vIRF1 has been discovered to mediate cellular metabolism by recruiting the Kelch-like 3 (KLHL3) E3 ligase, which facilitates the formation of the KLHL3-Cullin-3 E3 ubiquitin ligase complex [ 108 ]. This complex mediates proteasomal degradation of the heterogeneous nuclear ribonuclear protein Q1 (hnRNP Q1), leading to reduced glycerophosphodiester phosphodiesterase domain containing 1 (GDPD1) mRNA expression, an associated increase in aerobic glycolysis, and the onset of the Warburg Effect [ 108 ].…”

Section: Gammaherpesvirusesmentioning

confidence: 99%

“…vIRF1 has been discovered to mediate cellular metabolism by recruiting the Kelch-like 3 (KLHL3) E3 ligase, which facilitates the formation of the KLHL3-Cullin-3 E3 ubiquitin ligase complex [ 108 ]. This complex mediates proteasomal degradation of the heterogeneous nuclear ribonuclear protein Q1 (hnRNP Q1), leading to reduced glycerophosphodiester phosphodiesterase domain containing 1 (GDPD1) mRNA expression, an associated increase in aerobic glycolysis, and the onset of the Warburg Effect [ 108 ]. This step is critical for KSHV survival as treatment with glycolytic inhibitors induced apoptosis in KSHV-infected endothelial cells [ 153 ].…”

Section: Gammaherpesvirusesmentioning

confidence: 99%

E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation

Oswald,

Constantine,

Adegbuyi

et al. 2023

Viruses

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For productive infection and replication to occur, viruses must control cellular machinery and counteract restriction factors and antiviral proteins. Viruses can accomplish this, in part, via the regulation of cellular gene expression and post-transcriptional and post-translational control. Many viruses co-opt and counteract cellular processes via modulation of the host post-translational modification machinery and encoding or hijacking kinases, SUMO ligases, deubiquitinases, and ubiquitin ligases, in addition to other modifiers. In this review, we focus on three oncoviruses, Epstein–Barr virus (EBV), Kaposi’s sarcoma herpesvirus (KSHV), and human immunodeficiency virus (HIV) and their interactions with the ubiquitin–proteasome system via viral-encoded or cellular E3 ubiquitin ligase activity.

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A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA

Cited by 8 publications

References 75 publications

Lactylation of NAT10 promotes N4‐acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation

Lactylation of NAT10 promotes N4‐acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation

Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol

E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation

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