Understanding the interplay between N6‐methyladenine RNA methylation and noncoding RNAs in kidney disease DOI Creative Commons

Saiya Zhu,

Dong Zhou

Clinical and Translational Discovery, Journal Year: 2023, Volume and Issue: 3(5)

Published: Sept. 29, 2023

First discovered in 1974,1 N6-methyladenosine (m6A) is the most prevalent epigenetic modification eukaryotic mRNAs at posttranscriptional level under pathophysiological conditions. The m6A entails methylation of adenine nitrogen 6 (N6) position. Three classes enzymes mediate process modification, including RNA methyltransferases (writers), demethylases (erasers), and recognition proteins (readers).2 Writers can form a multicomponent methyltransferase complex (MTC) that catalyzes by transferring methyl groups to RNA. In MTC, METTL3, METTL14 WTAP are core components. Serving as erasers, name implies, (FTO ALKBH5) responsible for removing S-adenosyl methionine from adenines At same time, readers (YTHDF, YTHDC eIF3) recognize m6A-modified RNAs bind subsequently determining fate Therefore, considered invertible dynamic. recent years, advent advanced high-throughput sequencing has facilitated identification m6A. general, presents 0.4%−0.6% all cellular RNAs, mRNAs, noncoding (ncRNAs), circular (circRNAs).3 publication Clinical Translational Medicine, Ni et al. reported METTL3 promoted Ena/VASP-like (EVL) mRNA activated transforming growth factor-beta 1 (TGF-β1) signalling pathway, which ultimately aggravated kidney fibrosis.4 Beyond regulating mRNA-coding genes, exhibited remarkable capacity modulating function ncRNAs dictate after various insults, especially carcinoma. Conversely, also participate regulation amid disease progression. fully understanding crosstalk between will supplement piece puzzle pathogenesis non-tumour diseases shed light on developing effective therapeutic strategies these medical catastrophes. ncRNAs, mainly comprised micro (miRNAs), long (lncRNAs), circRNAs, account large class transcripts mammalian genomes without protein-coding potential. Despite this, they crucial regulators diverse physiological pathological processes. controls stability, processing, transport. As illustrated Figure 1, accumulating studies have shown cause disorders through multiple dysregulated pathways diseased kidneys. Because evidence circRNAs remains lacking, we focus introducing role miRNAs lncRNAs system. make up majority miRNA diverse. For instance, vitro, positively modulated miR-873-5p attenuate oxidative stress apoptosis Keap1/Nrf2 pathway cultured proximal tubular cells stimulated with colistin.5 vivo, METTL3-mediated miR-21-5p maturation. Matured SPRY1/ERK/NF-κB axis obstructive kidneys, exacerbating inflammation driving fibrosis.6 depicted findings, may exert opposite regulatory roles different stages obtaining full image required elucidate mechanisms in-depth their impact development disease. comparison, lncRNA was found regulate gene expression via interacting molecules, protein post-translational modifications, or remodelling chromatin states despite lacking an open reading framework. participates biogenesis regulates numerous cell activities. glomerulonephritis tissues, increased. To profile landscape glomerular cells, mouse mesangial were lipopolysaccharide, then subjected methylated immunoprecipitation identified 1141 differential m6A-methylated lncRNAs. These lncRNA-targeted enriched NF-KB, MAPK, Toll-like receptor signaling pathways. Knockdown drastically reduced levels methylation, cytokines interleukin tumour necrosis factor-α, inhibited proliferation cycle results laid basis further glomerulonephritis.7 Besides diseases, m6A-induced MALAT1 fibrosis activating miR-145/FAK nephropathy.8 Impressively, demethylase FTO epithelial-mesenchymal transition reducing GAS5. addition, although signature been used early diagnosis prognosis prediction, occurrence carcinoma unclear. mentioned above, mutually regulated. Mechanistically, modulate binding 3′UTR m6A-related inhibiting translation. Unfortunately, current non-tumor not robust. Among existing miRNAs, miR-155 potential new biomarker monitoring progression lupus nephritis (LN) LN targeting regulators.9 clear carcinoma, negatively regulated 3′ UTR FTO, eraser m6A, increased level, apoptosis, enhanced proliferation.10 Similarly, miR-501-3p inhibit cancer decreasing m6A.11 Different often serve scaffolds target molecule stability. specific domains recruit writers, enhancing downstream mRNA. Amid progression, AI662270 binds CTGF promoter directly interacts increase consequently enhance stability mRNA.12 Certainly, possesses ability determine such stimulating PARP1 accelerating decay PARP1.13 summary, herein showed how diseases. Further interplay would undoubtedly provide novel perspectives comprehending intricate networks refractory syndromes, lead inevitable irreversible detrimental outcomes clinic. Given dynamic reversible provoked interest scenarios, expect bright future halting explicitly communications it might be journey. Dr. Zhou supported National Institutes Health grants DK116816, DK128529 DK132059. authors declare no conflict interest.

Language: Английский

N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential DOI Creative Commons
Yuting Sun, De Jin, Ziwei Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Journal Year: 2023, Volume and Issue: 1866(4), P. 194967 - 194967

Published: Aug. 6, 2023

The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as "writers," and demethylases, known "erasers," leading a dynamic reversible process. Changes in m6A levels have been implicated wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, splicing, establishing strong correlation with various diseases. Both physiologically pathologically, methylation plays critical role the initiation progression kidney disease. may also facilitate early diagnosis treatment diseases, according accumulating research. This review aims provide comprehensive overview potential mechanism well its application such There will be thorough examination mechanisms, paying particular attention interplay between writers, erasers, readers. Furthermore, this paper elucidate diseases methylation, summarize expression patterns pathological tissues, discuss therapeutic benefits targeting context

Language: Английский

Citations

10
N6-methyladenosine methylation in kidney injury DOI Creative Commons
Qimeng Wang,

Xiaoting Fan,

Qinghao Sheng

et al.

Clinical Epigenetics, Journal Year: 2023, Volume and Issue: 15(1)

Published: Oct. 21, 2023

Abstract Multiple mechanisms are involved in kidney damage, among which the role of epigenetic modifications occurrence and development diseases is constantly being revealed. However, N6-methyladenosine (M6A), a well-known post-transcriptional modification, has been regarded as most prevalent higher eukaryotic, various biological processes cells such maintaining stability mRNA. The M6A modification mechanism damage attracted widespread attention. In this review, we mainly summarize progression from following aspects: regulatory pattern N6-methyladenosine, critical roles chronic disease, acute injury renal cell carcinoma, then reveal its potential significance diagnosis treatment diseases. A better understanding field will be helpful for future research clinical

Language: Английский

Citations

10
Inhibition of METTL3 promotes mesangial cell mitophagy and attenuates glomerular damage by alleviating FOSL1 m6A modifications via IGF2BP2-dependent mechanisms DOI
Tao Liu,

Xing Xing Zhuang,

Xiao Zhu

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116867 - 116867

Published: March 1, 2025

Language: Английский

Citations

0
The role of N-methyladenosine modification in acute and chronic kidney diseases DOI Creative Commons

Saiqi Qi,

Jie Song, Linjun Chen

et al.

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: Dec. 8, 2023

Abstract N 6-methyladenosine (m6A) modification is a kind of RNA in which methylation occurs at the sixth position adenosine RNA, can occur various RNAs such as mRNAs, lncRNAs and miRNAs. This one most prominent frequent posttranscriptional modifications within organisms has been shown to function dynamically reversibly variety ways, including splicing, export, attenuation translation initiation efficiency regulate expression. There are three main enzymes associated with m6A modification: writers, readers erasers. Increasing evidence that onset development kidney disease. In this article, we address important physiological pathological roles diseases (uremia, ischemia–reperfusion injury, drug-induced diabetic nephropathy) its molecular mechanisms provide reference for diagnosis clinical management diseases.

Language: Английский

Citations

9
METTL3 modification of circStk4 affects mouse glomerular messangial cell autophagy, proliferation and apotosis by regulating miR-133a-3p/C1 axis DOI
Xiujuan Qin, Huiyu Chen,

Wenjia Zheng

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111091 - 111091

Published: Feb. 6, 2024

Language: Английский

Citations

2
Identification of Rab7 as an autophagy marker: potential therapeutic approaches and the effect of Qi Teng Xiao Zhuo granule in chronic glomerulonephritis DOI Creative Commons
Xiujuan Qin, Huiyu Chen,

Xiaoli Zhu

et al.

Pharmaceutical Biology, Journal Year: 2023, Volume and Issue: 61(1), P. 1120 - 1134

Published: July 21, 2023

Context Qi Teng Xiao Zhuo granule (QTXZG) is a traditional Chinese medicine (TCM) used for therapeutic effects on chronic glomerulonephritis (CGN). However, the underlying mechanism remains unclear.Objective To investigate molecular of QTXZG CGN by proteomics.Materials and methods The model was induced in Sprague–Dawley rats injecting adriamycin (3.5 mg/kg, Day 1; 3.0 14) twice through tail vein. Urine samples were collected 21st day; divided randomly into control, adriamycin, administration groups. Rats group received (10.8 g/kg); control groups given physiological saline once per day 30 days. Proteomics applied to identify candidate proteins combined with autophagy database verified immunofluorescence (IF) western blots (WB).Results 278 differentially expressed (DEPs) identified based proteomics Rab7 screened as an protein biomarker. In vitro cell experiments, we found that (20%, IC50 = 23.47%) could decrease expression NLRP3, Caspase-1, IL-18, IL-1β, while increasing Pink1, Parkin, Rab7, Podocalyxin. apoptosis rate increased from 6.68 ± 0.07 11.03 0.36%. Overexpression resulted increase relevant expression.Discussion conclusion TCM CGN-regulating herbs can exert affecting Rab7/Pink1/Parkin pathway promote mitochondrial autophagy. New breakthroughs targeted may eventually enable such applications.

Language: Английский

Citations

5
Overexpression of FTO inhibits excessive proliferation and promotes the apoptosis of human glomerular mesangial cells by alleviating FOXO6 m6A modification via YTHDF3-dependent mechanisms DOI Creative Commons

Xingxing Zhuang,

Tao Liu,

Liangbing Wei

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 26, 2023

Background: N6-methyladenosine (m6A) is a prevalent post-transcriptional modification presented in messenger RNA (mRNA) of eukaryotic organisms. Chronic glomerulonephritis (CGN) characterised by excessive proliferation and insufficient apoptosis human glomerular mesangial cells (HGMCs) but its underlying pathogenesis remains undefined. Moreover, the role m6A CGN poorly understood. Methods: The total level was detected using quantification assay (Colorimetric). Cell assessed EdU cell assay, flow cytometry. sequencing performed to screen downstream target fat mass obesity-associated protein (FTO). MeRIP-qPCR conducted detect forkhead box o6 (FOXO6) HGMCs. RIP utilized indicate targeting relationship between YTH domain family 3 (YTHDF3) FOXO6. Actinomycin D used investigate stability FOXO6 Results: study found that expression FTO significantly reduced lipopolysaccharide (LPS)-induced HGMCs renal biopsy samples patients with CGN. overexpression knockdown could regulate Furthermore, cellular experiments revealed as regulating Mechanistically, decreases reduces mRNA YTHDF3-dependent manner. Additionally, decreased inhibits PI3K/AKT signaling pathway, thereby inhibiting promoting Conclusion: This offers insights into mechanism through which regulates mediating mRNA. These findings also suggest potential diagnostic marker therapeutic for

Language: Английский

Citations

3
The Role of METTL3-mediated CircStk4 Modification in the Treatment of Chronic Glomerulonephritis with Qi Teng Xiao Zhuo Granule DOI
Xiujuan Qin, Huiyu Chen,

Wenjia Zheng

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156183 - 156183

Published: Oct. 28, 2024

Language: Английский

Citations

0
Methyltransferase-like 3 represents a prospective target for the diagnosis and treatment of kidney diseases DOI Creative Commons
Bin Song, Xiaolong Wu, Yan Zeng

et al.

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Nov. 14, 2024

Kidney disease is marked by complex pathological mechanisms and significant therapeutic hurdles, resulting in high morbidity mortality rates globally. A deeper understanding of the fundamental processes involved can aid identifying novel targets improving treatment efficacy. Current comprehensive data analyses indicate involvement methyltransferase-like 3 (METTL3) its role RNA N6-methyladenosine methylation various renal pathologies, including acute kidney injury, fibrosis, chronic disease. However, there a paucity thorough reviews that clarify functional METTL3 evaluate importance enhancing outcomes. This review seeks to systematically examine roles, mechanisms, potential clinical applications diseases. The findings presented suggest implicated etiology exacerbation disorders, affecting their onset, progression, malignancy, responsiveness chemotherapeutic agents through regulation specific genetic pathways. In conclusion, this underscores detrimental correlation between diseases, highlighting promise targeting METTL3. Additionally, it offers critical insights for researchers concerning diagnosis, prognosis, strategies conditions.

Language: Английский

Citations

0
m6A Ribonucleic Acid Methylation in Fibrotic Diseases of Visceral Organs DOI Creative Commons

Xiaoniu Dai,

Yusi Cheng, Wei Luo

et al.

Small Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Fibrosis is a pathological process characterized by the excessive deposition of extracellular matrix in tissue's space, leading to structural injury and organ dysfunction, even failure, posing threat human life. Despite mounting evidence suggesting that fibrosis reversible, effective treatments for fibrotic diseases are lacking. Accumulating has elucidated ribonucleic acid (RNA) modifications have emerged as novel mechanisms regulating gene expression. N6‐methyladenosine (m6A) modification well‐known prevalent RNA posttranscriptional participates essential biological processes such splicing, translation, degradation. It tightly implicated wide range cellular various diseases, particularly fibrosis. The m6A dynamic reversible regulated methylases, commonly known “writers,” demethylases referred “erasers,” while recognized “readers.” suggests on RNAs associated with visceral organs including lungs, heart, liver, kidney. In this review, recent advances impact methylation highlighted potential prospects therapy treating discussed.

Language: Английский

Citations

0