Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells

Honda, Takeshi; Nishimura, Kensuke; Teng, Da; Takemoto, Kazuhiro; Ueda, Keiji

doi:10.1038/s41598-020-79197-y

Cited by 10 publications

(7 citation statements)

References 33 publications

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“…Human LINE1 antisense promoter driven transcripts are transcribed in a variety of cell types, comprising ~4% of all human genes [ 628 ]. The activation of LINE1 (L1) and L1 antisense promoter (ASP) that drive mRNA production and L1-gene chimeric RNA production, respectively, are associated with a wide range of pathologies, including cancer and genetic diseases [ 629 , 630 , 631 , 632 , 633 , 634 ].…”

Section: Melatonin Regulates Sars-cov-2-mediated Crosstalk Between Th...mentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

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The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m6A methylome, and can trigger the derepression of long interspersed nuclear element 1 (LINE1), resulting in global hypomethylation, epigenetic changes, and genomic instability. The timely application of melatonin during early infection enhances host innate antiviral immune responses by preventing the formation of “viral factories” by nucleocapsid liquid-liquid phase separation that effectively blockades viral genome transcription and packaging, the disassembly of stress granules, and the sequestration of DEAD-box RNA helicases, including DDX3X, vital to immune signaling. Melatonin prevents membrane depolarization and protects cristae morphology to suppress glycolysis via antioxidant-dependent and -independent mechanisms. By restraining the derepression of LINE1 via multifaceted strategies, and maintaining the balance in m6A RNA modifications, melatonin could be the quintessential ancient molecule that significantly influences the outcome of the constant struggle between virus and host to gain transcriptomic and epitranscriptomic dominance over the host genome during acute infection and PASC.

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Section: Melatonin Regulates Sars-cov-2-mediated Crosstalk Between Th...mentioning

confidence: 99%

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh¹,

Reíter

2022

IJMS

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“…L1 can lead to retrotransposition of L1 itself and other mobile elements, such as Alu and SVA (Dewannieux et al, 2003; Raiz et al, 2012). Although its biological significance remains unclear, L1 is also hypothesized to contribute to biological processes; for example, the L1 antisense promoter plays a role in cell proliferation (T. Honda et al, 2020). On the other hand, L1 dysregulation has detrimental effects on health and host genome stability, with multiple studies linking L1 to various cancers (T. Honda, 2016; Kemp & Longworth, 2015; Sciamanna et al, 2014; Sciamanna et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Cap Analysis of Gene Expression Clarifies Transcriptomic Divergence Within Monozygotic Twin Pairs

Katoh,

Asai,

Takemoto

et al. 2023

Twin Res Hum Genet

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Phenotypic variation is the result of gene expression based on complex interaction between genetic and environmental factors. It is well known that genetic and environmental factors influence gene expression, but our understanding of their relative importance remains limited. To obtain a hint for the understanding of their contributions, we took advantage of monozygotic twins, as they share genetic and shared environmental factors but differ in nonshared factors, such as environmental differences and stochastic factors. In this study, we performed cap analysis of gene expression on three pairs of twins and clustered each individual based on their expression profiles of annotated genes. The dendrogram of annotated gene transcripts showed a monophyletic clade for each twin pair. We also analyzed the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), given their abundance in the genome. Clustering analyses demonstrated that HERV and LINE expression diverged even within monozygotic twin pairs. Thus, HERVs and LINEs are more susceptible to nonshared factors than annotated genes. Motif analysis of differentially expressed annotated genes suggests that specificity protein/Krüppel-like factor family transcription factors are involved in the expression divergence of annotated gene influenced by nonshared factors. Collectively, our findings suggest that expressions of annotated genes and retrotransposons are differently regulated, and that the expression of retrotransposons is more susceptible to nonshared factors than annotated genes.

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“…Then, reverse-transcription was performed using a Verso cDNA Synthesis Kit (Thermo Fisher Scientific, Waltham, MA, USA) with oligo-dT primers or a huP2Br genome-specific primer (MH49). RT-qPCR assays for the GAPDH [ 84 ], the HPRT1 [ 85 ], the L3MBTL1 [ 59 ], and BoDV-1 N mRNAs were carried out using THUNDERBIRD Next SYBR (TOYOBO, Osaka, Japan) and gene-specific primers with the CFX Connect Real-Time PCR Detection System (Bio-Rad Laboratories, Hercules, CA, USA). RT-qPCR assays for BoDV-1 genomic RNA (gRNA) and BoDV-1 M/G/L mRNAs were carried out using THUNDERBIRD Next Probe qPCR Mix (TOYOBO) and the BoDV-1-specific primers and probes.…”

Section: Methodsmentioning

confidence: 99%

Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System

Sasaki,

Ogawa,

Katoh

et al. 2024

IJMS

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Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system.

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Effects of activation of the LINE-1 antisense promoter on the growth of cultured cells

Cited by 10 publications

References 33 publications

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Cap Analysis of Gene Expression Clarifies Transcriptomic Divergence Within Monozygotic Twin Pairs

Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System

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