N6-Adenosine Methylation of Socs1 mRNA Is Required to Sustain the Negative Feedback Control of Macrophage Activation

Du, Jie; Liao, Wang; Liu, Weicheng; Deb, Dilip K.; He, Lei; Hsu, Phillip J.; Nguyen, Tivoli; Zhang, Linda; Bissonnette, Marc; He, Chuan; Li, Yan Chun

doi:10.1016/j.devcel.2020.10.023

Cited by 72 publications

(82 citation statements)

References 103 publications

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“… 78 Research shows that knockout of METTL14 depletion blunts Socs1 m6A methylation and reduces YTHDF1 binding to m6A sites, and m6A-mediated SOCS1 induction plays a critical role in maintaining the negative feedback control of macrophage activation in response to bacterial infection. 79 All studies indicated that YTHDF1 could recognize m6A-modified viral RNA and mediate its expression.…”

Section: The Roles Of Ythdf1 In Other Nontumor Diseasesmentioning

confidence: 99%

The roles and mechanisms of the m6A reader protein YTHDF1 in tumor biology and human diseases

Chen

Zhong

Xia

et al. 2021

Molecular Therapy - Nucleic Acids

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Section: The Roles Of Ythdf1 In Other Nontumor Diseasesmentioning

confidence: 99%

The roles and mechanisms of the m6A reader protein YTHDF1 in tumor biology and human diseases

Chen

Zhong

Xia

et al. 2021

Molecular Therapy - Nucleic Acids

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“…Jian et al demonstrated that Mettl14 enhances the transcription factor FOXO1 by increasing its translation, not RNA stabilization, in endothelial in ammation [15]. In bacterial infection, Mettl14 depletion blocked m 6 A methylation of SOCS1, diminishing its RNA stability [10]. In addition, Mettl14 forms a complex with Mettl3, called the Mettl3/Mettl14 complex, modifying nascent transcripts whose translation is enhanced [14].…”

Section: Discussionmentioning

confidence: 99%

Mettl14 Mediates the Inflammatory Response of Macrophages in Atherosclerosis Through the NF-κB/IL-6 Signaling Pathway

Yang

Ran

et al. 2021

Preprint

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The inflammatory response of macrophages has been reported to play a critical role in atherosclerosis. The inflammatory state of macrophages is modified by epigenetic reprogramming. m6A RNA methylation is an epigenetic modification of RNAs. However, little is known about the potential roles and underlying mechanisms of m6A modification in macrophage inflammation. Herein, we showed that the expression of the m6A modification “writer” Mettl14 was increased in coronary heart disease and LPS-stimulated THP-1 cells. Knockdown of Mettl14 promoted M2 polarization of macrophages, inhibited foam cell formation and decreased migration. Mechanistically, the expression of Myd88 and IL-6 was decreased in Mettl14 knockdown cells. Through m6A modification, Mettl14 regulated the stability of Myd88 mRNA. Furthermore, Myd88 affected the transcription of IL-6 via the distribution of p65 in nuclei rather than directly regulating the expression of IL-6 through m6A modification. In vivo, Mettl14 gene knockout significantly reduced the inflammatory response of macrophages and the development of atherosclerotic plaques. Taken together, our data demonstrate that Mettl14 plays a vital role in macrophage inflammation in atherosclerosis via the NF-κB/IL-6 signaling pathway, suggesting that Mettl14 may be a promising therapeutic target for the clinical treatment of atherosclerosis.

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“…Overexpressing SOCS1 under METTL14 or YTHDF1 rescued the phenotype of macrophage activation in vitro and in vivo . Accordingly, FTO showed an antagonistic role of METTL14 in regulating macrophage activity ( Du et al, 2020 ). Besides, METTL14 interacted with FOXO1 and acted directly on the promoter regions of VCAM-1 and ICAM-1, which enhanced monocyte binding to endothelial cells during atherosclerosis ( Jian et al, 2020 ).…”

Section: N6-methyladenosine Modification In Mediating Inflammation Responsesmentioning

confidence: 99%

Novel Insights Into the Potential Mechanisms of N6-Methyladenosine RNA Modification on Sepsis-Induced Cardiovascular Dysfunction: An Update Summary on Direct and Indirect Evidences

Wang

Peng

et al. 2021

Front. Cell Dev. Biol.

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Sepsis is a life-threatening organ dysfunction caused by a host’s dysfunctional response to infection. As is known to all, septic heart disease occurs because pathogens invading the blood stimulate the activation of endothelial cells, causing a large number of white blood cells to accumulate and trigger an immune response. However, in severe sepsis, the hematopoietic system is inhibited, and there will also be a decline in white blood cells, at which time the autoimmune system will also be suppressed. During the immune response, a large number of inflammatory factors are released into cells to participate in the inflammatory process, which ultimately damages cardiac myocytes and leads to impaired cardiac function. N6-methyladenosine (m6A) is a common RNA modification in mRNA and non-coding RNA that affects RNA splicing, translation, stability, and epigenetic effects of some non-coding RNAs. A large number of emerging evidences demonstrated m6A modification had been involved in multiple biological processes, especially for sepsis and immune disorders. Unfortunately, there are limited results provided to analyze the association between m6A modification and sepsis-induced cardiovascular dysfunction (SICD). In this review, we firstly summarized current evidences on how m6A mediates the pathophysiological process in cardiac development and cardiomyopathy to emphasize the importance of RNA methylation in maintaining heart biogenesis and homeostasis. Then, we clarified the participants of m6A modification in extended inflammatory responses and immune system activation, which are the dominant and initial changes secondary to sepsis attack. After that, we deeply analyzed the top causes of SICD and identified the activation of inflammatory cytokines, endothelial cell dysfunction, and mitochondrial failure. Thus, the highlight of this review is that we systematically collected all the related potential mechanisms between m6A modification and SICD causes. Although there is lack of direct evidences on SICD, indirect evidences had been demonstrated case by case on every particular molecular mechanism and signal transduction, which require further explorations into the potential links among the listed mechanisms. This provides novel insights into the understanding of SICD.

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N6-Adenosine Methylation of Socs1 mRNA Is Required to Sustain the Negative Feedback Control of Macrophage Activation

Cited by 72 publications

References 103 publications

The roles and mechanisms of the m6A reader protein YTHDF1 in tumor biology and human diseases

The roles and mechanisms of the m6A reader protein YTHDF1 in tumor biology and human diseases

Mettl14 Mediates the Inflammatory Response of Macrophages in Atherosclerosis Through the NF-κB/IL-6 Signaling Pathway

Novel Insights Into the Potential Mechanisms of N6-Methyladenosine RNA Modification on Sepsis-Induced Cardiovascular Dysfunction: An Update Summary on Direct and Indirect Evidences

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