METTL3-mediated m6A mRNA methylation regulates neutrophil activation through targeting TLR4 signaling

Luo, Sheng; Liao, Chaoxiong; Zhang, Lina; Ling, Chunxiu; Zhang, Xuedi; Xie, Pengyun; Su, Guomei; Chen, Zhanghui; Zhang, Liangqing; Lai, Tianwen; Tang, Jing

doi:10.1016/j.celrep.2023.112259

Cited by 28 publications

(23 citation statements)

References 40 publications

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“…430−432 m6A modification has also been introduced into the mRNA of TLR4, leading to increased translation and down-regulated degradation, resulting in elevated protein levels and improved TLR4 signaling activation of neutrophils. 433 The use of the pseudouridine and m5Cmodified RALA mRNA nanocomplex has been shown to enhance the potency of cytolytic T cell responses. 434 In addition, mRNA modification by m5C plays a key role in transcription, RNA stability, and translational regulation.…”

Section: Chemical Modifications On Mrnamentioning

confidence: 99%

“…Moreover, m6A modification affects mRNA stability, localization, nuclear export, splicing, and translation. RNA immunoprecipitation assay has been employed to demonstrate the modification of m6A on PD-L1 mRNA, providing a means to regulate PD-L1 expression through RNA modification. − m6A modification has also been introduced into the mRNA of TLR4, leading to increased translation and down-regulated degradation, resulting in elevated protein levels and improved TLR4 signaling activation of neutrophils . The use of the pseudouridine and m5C-modified RALA mRNA nanocomplex has been shown to enhance the potency of cytolytic T cell responses .…”

Section: Chemical Modifications On Rna Molecules In Preclinical Researchmentioning

confidence: 99%

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Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration. CONTENTS1. Introduction 930 2. Current Status and Challenges of RNA Therapeutics in Clinics 933 2.1. Molecular Mechanisms and Clinical Research Progress of RNAs 934 2.1.1. ASO 934 2.1.2. siRNA 934 2.1.3. Aptamer 936 2.1.4. mRNA 936 2.1.5. RNA Therapeutics on the Cusp of Clinical Breakthroughs 938 2.2. Major Challenges of Current RNA Therapeutics in Clinics 940 2.

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Section: Chemical Modifications On Mrnamentioning

confidence: 99%

Section: Chemical Modifications On Rna Molecules In Preclinical Researchmentioning

confidence: 99%

Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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“…m6A mRNA modification may be involved in the regulation of neutrophil migration and inflammatory response with therapeutic implications [57, 58]. Further research is needed to clarify specific pathways and targets.…”

Section: M6a and Neutrophilsmentioning

confidence: 99%

“…IL-1β and TNFα secreted by complement C5a receptor 1 (C5aR1)-positive neutrophils may stabilize WTAP via phosphorylation, which promoted breast cancer proliferation in vivo via increased m6A methylation of enolase 1 (Eno1) RNA and enhanced glycolytic activity [61]. m6A mRNA modification may be involved in the regulation of neutrophil migration and inflammatory response with therapeutic implications [57,58]. Further research is needed to clarify specific pathways and targets.…”

Section: M6a and Neutrophilsmentioning

confidence: 99%

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N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases

Teng,

Yi,

Chen

et al. 2023

J Innate Immun

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The post-transcriptional N6-methyladenosine (m6A) modification of RNA influences stability, transport, and translation with implications for various physiological and pathological processes. Immune cell development, differentiation, and activation are also thought to be regulated by m6A and affect host defense against pathogens and inflammatory response with impacts on infectious, neoplastic, autoimmune, cardiovascular, hepatic, and osteal diseases. The current review summarizes recent research on m6A in monocyte/macrophages, neutrophils, dendritic cells, natural killer cells, and microglia and gives insights into epigenetic modifications of the immune system and novel therapeutic strategies for immune-related diseases.

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Role of N6‐methyladenosine RNA modification in cancer

Qu,

Gao,

Zhang

et al. 2024

MedComm

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N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer‐associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism‐associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.

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METTL3-mediated m6A mRNA methylation regulates neutrophil activation through targeting TLR4 signaling

Cited by 28 publications

References 40 publications

Chemically Modified Platforms for Better RNA Therapeutics

Chemically Modified Platforms for Better RNA Therapeutics

N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases

Role of N6‐methyladenosine RNA modification in cancer

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