RNA m6A modification and its function in diseases

Tong, Jiyu; Flavell, Richard A.; Li, Hua Bing

doi:10.1007/s11684-018-0654-8

Cited by 205 publications

(188 citation statements)

References 70 publications

(114 reference statements)

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“…METTL3 is also known as MTA70, which is originally identified as a methyltransferase involved in the process of m 6 A methylation [29]. Accumulated evidence has strongly supported that METTL3 is involved in a variety of physiological contexts and in cancers [30][31][32]. METTL3 is located in a nuclear speckle, which reveals that METTL3 may play an important role in RNA metabolism [33,34].…”

Section: Discussionmentioning

confidence: 99%

METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway

Wang

Yan

et al. 2019

Mediators of Inflammation

142

121

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Methyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mechanism of METTL3 in rheumatoid arthritis (RA). The aim of the present study is to elucidate the function and potential mechanism of METTL3 in RA pathogenesis. We used quantitative real-time polymerase chain reaction to detect the expression of METTL3 in RA patients and controls as well as the macrophage cell line. CCK-8 was used for cell proliferation assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to estimate the generation of IL-6 and TNF-α in macrophages. Western blot and immunofluorescence were applied to evaluate the activation of NF-κB in macrophages. The expression of METTL3 was significantly elevated in patients with RA. It was positively associated with CRP and ESR, two common markers for RA disease activity. Besides, LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages. Moreover, the effect of METTL3 on LPS-induced inflammation in macrophages was dependent on NF-κB. This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.

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Section: Discussionmentioning

confidence: 99%

METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway

Wang

Yan

et al. 2019

Mediators of Inflammation

142

121

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“…The m6A motif base sequence in which METTL14 binds to mRNA was mainly GGACU, which was located in the junction between the coding sequence (CDS) and 3 ′ -untranslated region (3′-UTR) of mRNAs (Figures 3(c) and 3(d)). EIF3A could act as an m6A reader to participate in m6A RNA modification progression [22]. EIF3A mRNA expression in KIRC tissues was lower than that in normal kidney tissues.…”

Section: Patients With Lower Mettl14 Expression Had a Worsementioning

confidence: 95%

Identification of METTL14 in Kidney Renal Clear Cell Carcinoma Using Bioinformatics Analysis

et al. 2019

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The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80–90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAportal were applied to investigate the METTL14 mRNA expression in different tissues and KIRC stages. The Human Protein Atlas was used to verify the location of METTL14 in KIRC tissues. The main microRNAs (miRNAs) related to KIRC were analyzed using OncoLnc and starBase, while corresponding circular RNAs (circRNAs) interacting with miRNAs were predicted via circBank; then, the METTL14-miRNA-circRNA interaction network was established. The level of methyltransferase-like 14 (METTL14) mRNA was significantly lower in KIRC tissues compared with normal kidney tissues, which was relative to clinical and pathological stages. circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the KIRC progression. METTL14 mRNA is likely to regulate PTEN mRNA expression via changing its m6A RNA modification level. METTL14 mRNA expression negatively correlated with the KIRC stages and positively correlated with KIRC patients’ overall survival, which has great potential to serve as a clinical biomarker in KIRC.

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“…The fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5) are categorized as "erasers" which selectively remove the methyl code from target RNAs and reverse the methylation. YT521-B homology (YTH) domain-containing protein, eukaryotic translation initiation factor 3 (eIF3), IGF2 mRNA binding proteins (IGF2BP) families, and heterogeneous nuclear ribonucleoprotein (HNRNP) protein families are categorized as "readers" which decode m 6 A methylation and generate a functional signal (6,14). Thus, m 6 A may affect RNAs splicing, stability, transcription, and translation (15) as shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

et al. 2019

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Methyltransferase-like 3 (METTL3), a predominantly catalytic enzyme in the N 6 -methyladenosine (m 6 A) methyltransferase system, is dysregulated and plays a dual role (oncogene or tumor suppressor) in different human cancers. The expression and pro-or anticancer role of METTL3 in different cancers remain controversial. METTL3 is implicated in many aspects of tumor progression, including tumorigenesis, proliferation, invasion, migration, cell cycle, differentiation, and viability. Most underlying mechanisms involve multiple signaling pathways that rely on m 6 A-dependent modification. However, METTL3 can also modulate the cancer process by directly promoting the translation of oncogenes via interaction with the translation initiation machinery through recruitment of eukaryotic translation initiation factor 3 subunit h (eIF3h). In this review, we summarized the current evidence on METTL3 in diverse human malignancies and its potential as a prognostic/ therapeutic target.

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RNA m6A modification and its function in diseases

Cited by 205 publications

References 70 publications

METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway

METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway

Identification of METTL14 in Kidney Renal Clear Cell Carcinoma Using Bioinformatics Analysis

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

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