The N6-methyladenosine (m6A)-forming enzyme METTL3 facilitates M1 macrophage polarization through the methylation of STAT1 mRNA

Liu, Yihan; Liu, Zhujiang; Tang, Hao; Shen, Yicong; Zi-tong, Gong; Xie, Nan; Zhang, Xu; Wang, Wengong; Kong, Wei; Zhou, Yuan; Fu, Yi

doi:10.1152/ajpcell.00212.2019

Cited by 196 publications

(157 citation statements)

References 48 publications

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“…Often, the presence of atherosclerotic plaques correlates with inflammation and macrophages infiltration [43]. Recent work reported an epigenetic mechanism regulating macrophage function [44]. In this context, METTL3 methylated the signal transducer and activator of transcription 1 (STAT1) mRNA in M1 macrophages [44].…”

Section: Methylation Of Coding Rnas In Cardiovascular Diseasesmentioning

confidence: 99%

Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Mongelli

Atlante

Bachetti

et al. 2020

IJMS

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RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes in RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

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Section: Methylation Of Coding Rnas In Cardiovascular Diseasesmentioning

confidence: 99%

Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Mongelli

Atlante

Bachetti

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Often, in fact, the presence of atherosclerotic plaques correlates with inflammation and macrophages infiltration [38]. A recent work reported about an epigenetic mechanism regulating macrophage function [39]. In this context, METTL3 methylated the signal transducer and activator of transcription 1 (STAT1) mRNA in M1 macrophages [39].…”

Section: Introductionmentioning

confidence: 99%

“…A recent work reported about an epigenetic mechanism regulating macrophage function [39]. In this context, METTL3 methylated the signal transducer and activator of transcription 1 (STAT1) mRNA in M1 macrophages [39]. The regions of STAT1 more prone to modification were the coding sequence and the 3'-untranslated region overall increasing the relative mRNA stability [39].…”

Section: Introductionmentioning

confidence: 99%

“…In this context, METTL3 methylated the signal transducer and activator of transcription 1 (STAT1) mRNA in M1 macrophages [39]. The regions of STAT1 more prone to modification were the coding sequence and the 3'-untranslated region overall increasing the relative mRNA stability [39]. As a result, the methylation of STAT1 mRNA, increasing STAT1 translation and activity, seemed driving M1 macrophage polarization, defining a potentially novel anti-inflammatory signalling pathway [39], (see figure 4).…”

Section: Introductionmentioning

confidence: 99%

“…The regions of STAT1 more prone to modification were the coding sequence and the 3'-untranslated region overall increasing the relative mRNA stability [39]. As a result, the methylation of STAT1 mRNA, increasing STAT1 translation and activity, seemed driving M1 macrophage polarization, defining a potentially novel anti-inflammatory signalling pathway [39], (see figure 4). Positive effects have been reported on MAPK and STAT1 mRNAs whose translation was enhanced.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic Signalling and RNA Regulation in Cardiovascular Diseases

Mongelli¹,

Atlante²,

Bacchetti³

et al. 2019

Preprint

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RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

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The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ

Wang

Feng

et al. 2021

Advanced Science

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Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 2 (IGF2BP2)-deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. However, the IGF2BP2 −/− macrophages are refractory to interleukin-4 (IL-4) induced activation and alleviate cockroach extract induced pulmonary allergic inflammation. Molecular studies indicate that IGF2BP2 switches M1 macrophages to M2 activation by targeting tuberous sclerosis 1 via an N6-methyladenosine (m 6 A)-dependent manner. Additionally, it is also shown a signal transducer and activators of transcription 6 (STAT6)-high mobility group AT-hook 2-IGF2BP2-peroxisome proliferator activated receptor-axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases.

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The N⁶-methyladenosine (m⁶A)-forming enzyme METTL3 facilitates M1 macrophage polarization through the methylation of STAT1 mRNA

Cited by 196 publications

References 48 publications

Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

Epigenetic Signalling and RNA Regulation in Cardiovascular Diseases

The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ

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