N-6-methyladenosine RNA

The RNA modification N6-methyladenosine (m6A) is conserved across eukaryotes, and profoundly influences RNA metabolism, including regulating RNA stability. METTL3 and METTL14, together with several accessory components, form a 'writer' complex catalysing m6A modification. Conversely, FTO and ALKBH5 function as demethylases, rendering m6A dynamic. Key to understanding the functional significance of m6A is its 'reader' proteins, exemplified by YTH-domain-containing proteins (YTHDFs) canonical reader and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) non-canonical reader...

High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer by far. Herein, clinical HGSOC samples had higher N6 -methyladenosine (m6 A) modification than normal ovarian tissue, and its dysregulation had been reported to drive aberrant transcription and translation programs. However, Kringle containing transmembrane protein 2 (KREMEN2) and its m6 A modification have not been fully elucidated in HGSOC. In this study, the data from the high-throughput mRNA sequencing (RNA-seq) of clinical samples were processed using the weighted correlation network analysis (WGCNA) and functional enrichment analysis...

N 6 -methyladenosine (m6 A) is a prevalent internal modification in eukaryotic mRNA, tRNA, miRNA, and long non-coding RNA. It is also known for its role in plant responses to biotic and abiotic stresses. However, a comprehensive m6 A transcriptome-wide map for Puccinia striiformis f. sp. tritici ( Pst ) infections in wheat ( Triticum aestivum ) is currently unavailable. Our study is the first to profile m6 A modifications in wheat infected with a virulent Pst race. Analysis of RNA-seq and MeRIP-seq data revealed that the majority of differentially expressed genes are up-regulated and hyper-methylated...

N6 -methyladenosine (m6 A) is one of the most abundant chemical modifications in RNA and has vital significance in cellular processes and tumor development. However, the accurate analysis of site-specific m6 A modification remains a challenge. In this work, a MazF endoribonuclease activated rolling circle amplification (MazF-RCA) combined MALDI-TOF MS assay is developed for the detection of site-specific m6 A-RNA. MazF endoribonuclease can specifically cleave the ACA motif, leaving methylated (m6 A)CA motif intact...

OBJECTIVE: Asthma, a chronic inflammatory disease in which type 2 T helper cells (Th2) play a causative role in the development of T2 asthma. N6-methyladenosine (m6A) modification, an mRNA modification, and methyltransferase-like 3 (METTL3) is involved in the development of T2 asthma by inhibiting Th2 cell differentiation. Sex determining region Y-box protein 5 (SOX5) is involved in regulating T cell differentiation, but its role in T2 asthma was unclear. The objective of this study was to explore the role of METTL3 and SOX5 in T2 asthma and whether there is an interaction between the two...

BACKGROUND: The aim of this study was to investigate the effect of DNA methylation of Fork Head Box O3 (FOXO3a) on the process of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). METHODS: The expressions of FOXO3a, DNA methyltransferase 1 (DNMT1), METTL3, and EMT-related proteins (E-cadherin and N-cadherin) were measured. The influence of 5-Aza-dC and DNMT1 on the methylation level in the promoter region of FOXO3a was examined through the application of methylation-specific PCR (MSP)...

BACKGROUND: N6 -methyladenosine (m6 A) is a common modification in RNA, crucial for various cellular functions and associated with human diseases. Quantification of m6 A at single-base resolution is of great significance for exploring its biological roles and related disease research. However, existing analysis techniques, such as polymerase chain reaction (PCR) or loop-mediated isothermal amplification (LAMP), face challenges like the requirement for thermal cycling or intricate primer design...

N 6 -Methyladenosine (m6 A) is the most prevalent mRNA modification and is required for gene regulation in eukaryotes. ALKBH5, an m6 A demethylase, is a promising target, particularly for anticancer drug discovery. However, the development of selective and potent inhibitors of ALKBH5 rather than FTO remains challenging. Herein, we used a targeted covalent inhibition strategy and identified a covalent inhibitor, TD19, which selectively inhibits ALKBH5 compared with FTO demethylase in protein-based and tumor cell-based assays...

The N 6 -methyladenosine (m6 A) modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs. Accumulating evidence has suggested that m6 A methylation may be involved in the pathological process of major depressive disorder (MDD), a common neuropsychiatric disorder with an unclear aetiology. Here, we found that the levels of the circular RNA HECW2 (circHECW2) were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress (CUS) mouse model...

N(6)-methyladenosine (m6 A) critically regulates RNA dynamics in various biological processes. The m6 A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6 A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6 A from LATS2 mRNA, thereby stabilizing this transcript...

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC...

OBJECTIVE: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6 A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6 A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. METHODS: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database...

Certain environmental toxins are nucleic acid damaging agents, as are many chemotherapeutics used for cancer therapy. These agents induce various adducts in DNA as well as RNA. Indeed, most of the nucleic acid adducts (>90%) formed due to these chemicals, such as alkylating agents, occur in RNA 1 . However, compared to the well-studied mechanisms for DNA alkylation repair, the biological consequences of RNA damage are largely unexplored. Here, we demonstrate that RNA damage can directly result in loss of genome integrity...

Epitranscriptomic mechanisms, which constitute an important layer in post-transcriptional gene regulation, are involved in numerous cellular processes under health and disease such as stem cell development or cancer. Among various such mechanisms, RNA methylation is considered to have vital roles in eukaryotes primarily due to its dynamic and reversible nature. There are numerous RNA methylations that include, but are not limited to, 2'-O-dimethyladenosine (m6 Am), N 7 -methylguanosine (m7 G), N 6 -methyladenosine (m6 A) and N 1 -methyladenosine (m1 A)...

Elucidating the intricate interactions between viral pathogens and host cellular machinery during infection is paramount for understanding pathogenic mechanisms and identifying potential therapeutic targets. The RNA modification N6 -methyladenosine (m6 A) has emerged as a significant factor influencing the trajectory of viral infections. Hence, the precise and quantitative mapping of m6 A modifications in both host and viral RNA is pivotal to understanding its role during viral infection. With the rapid advancement of sequencing technologies, scientists are able to detect m6 A modifications with various quantitative, high-resolution, transcriptome approaches...

RNA methylation modifications are widespread in eukaryotes and prokaryotes, with N6 -methyladenosine (m6 A) the most common among them. Demethylases, including Fat mass and obesity associated gene (FTO) and AlkB homolog 5 (ALKBH5), are important in maintaining the balance between RNA methylation and demethylation. Recent studies have clearly shown that demethylases affect the biological functions of tumors by regulating their m6 A levels. However, their effects are complicated, and even opposite results have appeared in different articles...

Gastric cancer (GC) ranks third among cancers in terms of mortality rate worldwide. A clear understanding of the mechanisms underlying the genesis and progression of GC will contribute to clinical decision making. N6 -methyladenosine (m6 A) is the most abundant among diverse mRNA modification types and regulates multiple facets of RNA metabolism. In recent years, emerging studies have shown that m6 A modifications are involved in gastric carcinoma tumorigenesis and progression and can potentially be valuable new prospects for diagnosis and prognosis...

Many viruses, including foot-and-mouth disease virus (FMDV), can promote the degradation of host proteins through macroautophagy/autophagy, thereby promoting viral replication. However, the regulatory mechanism between autophagy and innate immune responses is not fully understood during FMDV infection. Here, we found that the host GTPBP4/NOG1 (GTP binding protein 4) is a negative regulator of innate immune responses. GTPBP4 deficiency promotes the antiviral innate immune response, resulting in the ability of GTPBP4 to promote FMDV replication...

Hepatocellular carcinoma (HCC), the most common form of primary liver cancers, accounts for a significant portion of cancer-related death globally. However, the molecular mechanisms driving the onset and progression of HCC are still not fully understood. Emerging evidence has indicated that non-protein-coding regions of genomes could give rise to transcripts, termed non-coding RNA (ncRNA), forming novel functional driving force for aberrant cellular activity. Over the past decades, overwhelming evidence has denoted involvement of a complex array of molecular function of ncRNAs at different stages of HCC tumorigenesis and progression...

The N6 -methyladenosine (m6 A) modification of RNA has been reported to remodel gene expression in response to environmental conditions; however, the biological role of m6 A in social insects remains largely unknown. In this study, we explored the role of m6 A in the division of labour by worker ants (Solenopsis invicta). We first determined the presence of m6 A in RNAs from the brains of worker ants and found that m6 A methylation dynamics differed between foragers and nurses. Depletion of m6 A methyltransferase or chemical suppression of m6 A methylation in foragers resulted in a shift to 'nurse-like' behaviours...