Browse
Submit Data
Databases
API
Help

Dataset Information

48 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

N6-Methyladenosine RNA Modification in Inflammation: Roles, Mechanisms, and Applications.

ABSTRACT: N6-methyladenosine (m6A) is the most prevalent internal mRNA modification. m6A can be installed by the methyltransferase complex and removed by demethylases, which are involved in regulating post-transcriptional expression of target genes. RNA methylation is linked to various inflammatory states, including autoimmunity, infection, metabolic disease, cancer, neurodegenerative diseases, heart diseases, and bone diseases. However, systematic knowledge of the relationship between m6A modification and inflammation in human diseases remains unclear. In this review, we will discuss the association between m6A modification and inflammatory response in diseases, especially the role, mechanisms, and potential clinical application of m6A as a biomarker and therapeutic target for inflammatory diseases.

SUBMITTER: Luo J

PROVIDER: S-EPMC8213350 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

N6-Methyladenosine RNA Modification in Inflammation: Roles, Mechanisms, and Applications.

Luo Jiahui J Xu Tao T Sun Kai K

Frontiers in cell and developmental biology 20210604

N6-methyladenosine (m6A) is the most prevalent internal mRNA modification. m6A can be installed by the methyltransferase complex and removed by demethylases, which are involved in regulating post-transcriptional expression of target genes. RNA methylation is linked to various inflammatory states, including autoimmunity, infection, metabolic disease, cancer, neurodegenerative diseases, heart diseases, and bone diseases. However, systematic knowledge of the relationship between m6A modification an ...[more]

PMID: 34150765

Similar Datasets

N6-methyladenosine Modification of Noncoding RNAs: Mechanisms and Clinical Applications in Cancer.

Project description:N6-methyladenosine (m6A) modification remains the most pivotal epigenetic modification on RNA. As we know, m6A not only affects physiological processes but is also involved in carcinoma. Noncoding RNAs play an indispensable role in the occurrence and development of carcinoma. However, a large amount of research is focused on mRNA currently. Insufficient research has been done on the relationship between noncoding RNA (ncRNA) methylation and cancer. Therefore, this review aims to introduce the theoretical knowledge of m6A modification in noncoding RNA, discuss its function in tumorigenesis and progression, and ultimately summarize its potential clinical applications.

| S-EPMC9776883 | biostudies-literature

N6-Methyladenosine Modification Controls Circular RNA Immunity.

Project description:Circular RNAs (circRNAs) are prevalent in eukaryotic cells and viral genomes. Mammalian cells possess innate immunity to detect foreign circRNAs, but the molecular basis of self versus foreign identity in circRNA immunity is unknown. Here, we show that N6-methyladenosine (m6A) RNA modification on human circRNAs inhibits innate immunity. Foreign circRNAs are potent adjuvants to induce antigen-specific T cell activation, antibody production, and anti-tumor immunity in vivo, and m6A modification abrogates immune gene activation and adjuvant activity. m6A reader YTHDF2 sequesters m6A-circRNA and is essential for suppression of innate immunity. Unmodified circRNA, but not m6A-modified circRNA, directly activates RNA pattern recognition receptor RIG-I in the presence of lysine-63-linked polyubiquitin chain to cause filamentation of the adaptor protein MAVS and activation of the downstream transcription factor IRF3. CircRNA immunity has considerable parallel to prokaryotic DNA restriction modification system that transforms nucleic acid chemical modification into organismal innate immunity.

| S-EPMC6778039 | biostudies-literature

Mechanism of RNA modification N6-methyladenosine in human cancer.

Project description:Since the breakthrough discoveries of DNA and histone modifications, the field of RNA modifications has gained increasing interest in the scientific community. The discovery of N6-methyladenosine (m6A), a predominantly internal epigenetic modification in eukaryotes mRNA, heralded the creation of the field of epi-transcriptomics. This post-transcriptional RNA modification is dynamic and reversible, and is regulated by methylases, demethylases and proteins that preferentially recognize m6A modifications. Altered m6A levels affect RNA processing, degradation and translation, thereby disrupting gene expression and key cellular processes, ultimately resulting in tumor initiation and progression. Furthermore, inhibitors and regulators of m6A-related factors have been explored as therapeutic approaches for treating cancer. In the present review, the mechanisms of m6A RNA modification, the clinicopathological relevance of m6A alterations, the type and frequency of alterations and the multiple functions it regulates in different types of cancer are discussed.

| S-EPMC7278081 | biostudies-literature

N6-methyladenosine RNA modification regulates photoperiod sensitivity in cotton.

Project description:The methylation of N6-methyladenosine (m6A) involves writers, erasers, and readers, acting synergistically in posttranscriptional regulation. These processes influence various biological processes, including plant floral transition. However, the specific role of m6A modifications in photoperiod sensitivity in cotton (Gossypium hirsutum) remains obscure. To elucidate this, in this study, we conducted transcriptome-wide m6A sequencing during critical flowering transition stages in the photoperiod-sensitive wild G. hirsutum var. yucatanense (yucatanense) and the photoperiod-insensitive cultivated cotton G. hirsutum acc. TM-1 (TM-1). Our results revealed significant variations in m6A methylation of 2 cotton varieties, with yucatanense exhibiting elevated m6A modification levels compared with TM-1 under long-day conditions. Notably, distinct m6A peaks between TM-1 and yucatanense correlated significantly with photoperiod sensitivity. Moreover, our study highlighted the role of the demethylase G. hirsutum ALKB homolog 5 (GhALKBH5) in modulating m6A modification levels. Silencing GhALKBH5 led to a decreased mRNA level of key photoperiodic flowering genes (GhADO3, GhAGL24, and GhFT1), resulting in delayed bud emergence and flowering. Reverse transcription quantitative PCR analyses confirmed that silencing GhADO3 and GhAGL24 significantly downregulated the expression of the floral integrator GhFT1. Collectively, our findings unveiled a transcriptional regulatory mechanism in which GhALKBH5-mediated m6A demethylation of crucial photoperiodic flowering transcripts modulated photoperiod sensitivity in cotton.

| S-EPMC11444288 | biostudies-literature

N6-methyladenosine RNA modification promotes viral genomic RNA stability and infection.

Project description:Molecular manipulation of susceptibility (S) genes that are antipodes to resistance (R) genes has been adopted as an alternative strategy for controlling crop diseases. Here, we show the S gene encoding Triticum aestivum m6A methyltransferase B (TaMTB) is identified by a genome-wide association study and subsequently shown to be a positive regulator for wheat yellow mosaic virus (WYMV) infection. TaMTB is localized in the nucleus, is translocated into the cytoplasmic aggregates by binding to WYMV NIb to upregulate the m6A level of WYMV RNA1 and stabilize the viral RNA, thus promoting viral infection. A natural mutant allele TaMTB-SNP176C is found to confer an enhanced susceptibility to WYMV infection through genetic variation analysis on 243 wheat varieties. Our discovery highlights this allele can be a useful target for the molecular wheat breeding in the future.

| S-EPMC9629889 | biostudies-literature

The Potential Roles of RNA N6-Methyladenosine in Urological Tumors

Project description:N6-methyladenosine (m6A) is regarded as the most abundant, prevalent and conserved internal mRNA modification in mammalian cells. M6A can be catalyzed by m6A methyltransferases METTL3, METTL14 and WTAP (writers), reverted by demethylases ALKBH5 and FTO (erasers), and recognized by m6A -binding proteins such as YTHDF1/2/3, IGF2BP1/2/3 and HNRNPA2B1 (readers). Emerging evidence suggests that m6A modification is significant for regulating many biological and cellular processes and participates in the pathological development of various diseases, including tumors. This article reviews recent studies on the biological function of m6A modification and the methylation modification of m6A in urological tumors.

| S-EPMC7510505 | biostudies-literature

Modification of N6-methyladenosine RNA methylation on heat shock protein expression.

Project description:This study was conducted to investigate effect of N6-methyladenosine (m6A) RNA methylation on Heat shock proteins (HSPs) and dissect the profile of HSP RNA methylation. The results showed that m6A methyltransferases METTL3 mRNA was decreased in responses to heat shock stress in HepG2 cells, but m6A-specific binding protein YTHDF2 mRNA was upregulated in a manner similar to HSP70 induction. Immunofluorescence staining showed that the majority of YTHDF2 was present in the cytosol, however, nearly all YTHDF2 translocated from the cytosol into the nucleus after heat shock. METTL3 knockdown significantly changed HSP70, HSP60, and HSP27 mRNA expression in HepG2 cells using siRNA, however, mRNA lifetime was not impacted. Silence of YTHDF2 using siRNA did not change expression of HSP70, but significantly increased HSP90, HSP60, and HSPB1 mRNA expression. In addition, m6A-seq revealed that HSP m6A methylation peaks are mainly enriched on exons and around stop codons, and shows a unique distribution profile in the 5'UTR and 3'UTR. Knockdown of METTL3 changed the methylation patterns of HSPs transcript. In conclusion, m6A RNA methylation regulates HSP gene expression. Differential expression of HSPs modulated by m6A may depend on the m6A site and abundance of the target gene. This finding provides insights into new regulatory mechanisms of HSPs in normal and stress situations.

| S-EPMC6002042 | biostudies-literature

N6-methyladenosine (m6A) modification in inflammation: a bibliometric analysis and literature review.

Project description:N6-methyladenosine (m6A) is the most abundant internal messenger RNA modification in eukaryotes, influencing various physiological and pathological processes by regulating RNA metabolism. Numerous studies have investigated the role of m6A in inflammatory responses and inflammatory diseases. In this study, VOSviewer and Citespace were used to perform bibliometric analysis to systematically evaluating the current landscape of research on the association between m6A and inflammation. The literature was sourced from the Web of Science Core Collection, with characteristics including year, country/region, institution, author, journal, citation, and keywords. According to the bibliometric analysis results of keywords, we present a narrative summary of the potential mechanisms by which m6A regulates inflammation. The results showed that the key mechanisms by which m6A modulates inflammation include apoptosis, autophagy, oxidative stress, immune cell dysfunction, and dysregulation of signaling pathways.

| S-EPMC11648684 | biostudies-literature

N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms.

Project description:As the most abundant and conserved internal modification in eukaryote RNAs, N6-methyladenosine (m6A) is involved in a wide range of physiological and pathological processes. The YT521-B homology (YTH) domain-containing family proteins (YTHDFs), including YTHDF1, YTHDF2, and YTHDF3, are a class of cytoplasmic m6A-binding proteins defined by the vertebrate YTH domain, and exert extensive functions in regulating RNA destiny. Distinct expression patterns of the YTHDF family in specific cell types or developmental stages result in prominent differences in multiple biological processes, such as embryonic development, stem cell fate, fat metabolism, neuromodulation, cardiovascular effect, infection, immunity, and tumorigenesis. The YTHDF family mediates tumor proliferation, metastasis, metabolism, drug resistance, and immunity, and possesses the potential of predictive and therapeutic biomarkers. Here, we mainly summary the structures, roles, and mechanisms of the YTHDF family in physiological and pathological processes, especially in multiple cancers, as well as their current limitations and future considerations. This will provide novel angles for deciphering m6A regulation in a biological system.

| S-EPMC10043241 | biostudies-literature

The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA.

Project description:RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.

| S-EPMC6954407 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data