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

Construction of chronic glomerulonephritis‑related lncRNA‑mRNA regulatory network and lncRNA‑­miRNA‑mRNA ceRNA network by bioinformatics analysis DOI Open Access

Xingxing Zhuang,

Tao Liu,

Liangbing Wei

et al.

Experimental and Therapeutic Medicine, Journal Year: 2023, Volume and Issue: 26(2)

Published: July 7, 2023

Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and also competitive binding to micro (mi)RNA, which is generally known as the endogenous RNA (ceRNA) network. The present study evaluated functional roles networks of lncRNAs in chronic glomerulonephritis (CGN). proliferative ability mouse glomerular mesangial cells (GMCs) induced by different concentrations lipopolysaccharide (LPS) was assessed using Cell Counting Kit-8 assay, sequencing (RNA-seq) performed identify differentially expressed LPS-induced GMCs. Based on results, six were selected for validation reverse transcription-quantitative PCR (RT-qPCR). Furthermore, network lncRNA-miRNA-mRNA ceRNA constructed assess role mechanism CGN-related lncRNAs. To elucidate biological functions lncRNAs, Gene Ontology (GO) process term enrichment Kyoto Encyclopedia Genes Genomes (KEGG) pathway analyses all mRNAs involved A total 1,532 including 594 upregulated 938 downregulated identified RNA-seq. results RT-qPCR consistent with RNA-seq results. An network, 236 556 mRNAs, 6 18 miRNAs 419 successfully constructed. GO KEGG demonstrated those often related inflammatory response substance metabolism. key GMCs, further global view CGN. These offered novel insights into pathogenesis CGN potential diagnostic biomarkers.

Language: Английский

Citations

0
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

Citations

0