Explore the vast range of titles available.

The epitranscriptomic mark N 6 -methyladenosine (m 6 A) is the most common type of messenger RNA (mRNA) post-transcriptional modification in eukaryotes. With the discovery of the demethylase FTO (FAT MASS AND OBESITY-ASSOCIATED PROTEIN) in Homo Sapiens , this modification has been proven to be dynamically reversible. With technological advances, research on m 6 A modification in plants also rapidly developed. m 6 A modification is widely distributed in plants, which is usually enriched near the stop codons and 3′-UTRs, and has conserved modification sequences. The related proteins of m 6 A modification mainly consist of three components: methyltransferases (writers), demethylases (erasers), and reading proteins (readers). m 6 A modification mainly regulates the growth and development of plants by modulating the RNA metabolic processes and playing an important role in their responses to environmental signals. In this review, we briefly outline the development of m 6 A modification detection techniques; comparatively analyze the distribution characteristics of m 6 A in plants; summarize the methyltransferases, demethylases, and binding proteins related to m 6 A; elaborate on how m 6 A modification functions in plant growth, development, and response to environmental signals; and provide a summary and outlook on the research of m 6 A in plants.

N6-methyladenosine (m 6 A) is the most prevalent and internal modification of eukaryotic mRNA. Multiple m 6 A methylation sites have been identified in the viral RNA genome and transcripts of DNA viruses in recent years. m 6 A modification is involved in all the phases of RNA metabolism, including RNA stability, splicing, nuclear exporting, RNA folding, translational modulation, and RNA degradation. Three protein groups, methyltransferases (m 6 A-writers), demethylases (m 6 A-erasers), and m 6 A-binding proteins (m 6 A-readers) regulate this dynamic reversible process. Here, we have reviewed the role of m 6 A modification dictating viral replication, morphogenesis, life cycle, and its contribution to disease progression. A better understanding of the m 6 A methylation process during viral pathogenesis is required to reveal novel approaches to combat the virus-associated diseases.

N 6 -methyladenosine (m 6 A) is the most abundant epigenetic modification of RNA, and its dysregulation drives aberrant transcription and translation programs that promote cancer occurrence and progression. Although defective gene regulation resulting from m 6 A often affects oncogenic and tumor-suppressing networks, m 6 A can also modulate tumor immunogenicity and immune cells involved in anti-tumor responses. Understanding this counterintuitive concept can aid the design of new drugs that target m 6 A to potentially improve the outcomes of cancer immunotherapies. Here, we provide an up-to-date and comprehensive overview of how m 6 A modifications intrinsically affect immune cells and how alterations in tumor cell m 6 A modifications extrinsically affect immune cell responses in the tumor microenvironment (TME). We also review strategies for modulating endogenous anti-tumor immunity and discuss the challenge of reshaping the TME. Strategies include: combining specific and efficient inhibitors against m 6 A regulators with immune checkpoint blockers; generating an effective programmable m 6 A gene-editing system that enables efficient manipulation of individual m 6 A sites; establishing an effective m 6 A modification system to enhance anti-tumor immune responses in T cells or natural killer cells; and using nanoparticles that specifically target tumor-associated macrophages (TAMs) to deliver messenger RNA or small interfering RNA of m 6 A-related molecules that repolarize TAMs, enabling them to remodel the TME. The goal of this review is to help the field understand how m 6 A modifications intrinsically and extrinsically shape immune responses in the TME so that better cancer immunotherapy can be designed and developed.

N 6 -methyladenosine (m 6 A), the most abundant modification in eukaryotic cells, regulates RNA transcription, processing, splicing, degradation, and translation. Circular RNA (circRNA) is a class of covalently closed RNA molecules characterized by universality, diversity, stability and conservatism of evolution. Accumulating evidence shows that both m 6 A modification and circRNAs participate in the pathogenesis of multiple diseases, such as cancers, neurological diseases, autoimmune diseases, and infertility. Recently, m 6 A modification has been identified for its enrichment and vital biological functions in regulating circRNAs. In this review, we summarize the role of m 6 A modification in the regulation and function of circRNAs. Moreover, we discuss the potential applications and possible future directions in the field.

N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects the fates of modified RNAs, including their stability, splicing, and/or translation, and thus plays important roles in posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute m6A deposition on distinct RNAs by their own or forming different complexes with additional partner proteins. In this review, we summarize the function of these m6A methyltransferases or complexes in regulating the key genes and pathways of cancer biology. We also highlight the progress in the use of m6A methyltransferases in mediating therapy resistance, including chemotherapy, targeted therapy, immunotherapy and radiotherapy. Finally, we discuss the current approaches and clinical potential of m6A methyltransferase-targeting strategies.

Divergent N 6 -methyladenosine (m 6 A) modifications are dynamic and reversible posttranscriptional RNA modifications that are mediated by m 6 A regulators or m 6 A RNA methylation regulators, i.e., methyltransferases (“writers”), demethylases (“erasers”), and m 6 A-binding proteins (“readers”). Aberrant m 6 A modifications are associated with cancer occurrence, development, progression, and prognosis. Numerous studies have established that aberrant m 6 A regulators function as either tumor suppressors or oncogenes in multiple tumor types. However, the functions and mechanisms of m 6 A regulators in cancer remain largely elusive and should be explored. Emerging studies suggest that m 6 A regulators can be modulated by epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, and lactylation or via noncoding RNA action, in cancer. This review summarizes the current roles of m 6 A regulators in cancer. The roles and mechanisms for epigenetic modification of m 6 A regulators in cancer genesis are segregated. The review will improve the understanding of the epigenetic regulatory mechanisms of m 6 A regulators.

Background Methylation of nucleotides, notably in the forms of 5-methylcytosine (5mC) in DNA and N 6 -methyladenosine (m 6 A) in mRNA, carries important information for gene regulation. 5mC has been elucidated to participate in the regulation of fruit ripening, whereas the function of m 6 A in this process and the interplay between 5mC and m 6 A remain uncharacterized. Results Here, we show that mRNA m 6 A methylation exhibits dynamic changes similar to DNA methylation during tomato fruit ripening. RNA methylome analysis reveals that m 6 A methylation is a prevalent modification in the mRNA of tomato fruit, and the m 6 A sites are enriched around the stop codons and within the 3′ untranslated regions. In the fruit of the ripening-deficient epimutant Colorless non-ripening ( Cnr ) which harbors DNA hypermethylation, over 1100 transcripts display increased m 6 A levels, while only 134 transcripts show decreased m 6 A enrichment, suggesting a global increase in m 6 A. The m 6 A deposition is generally negatively correlated with transcript abundance. Further analysis demonstrates that the overall increase in m 6 A methylation in Cnr mutant fruit is associated with the decreased expression of RNA demethylase gene SlALKBH2 , which is regulated by DNA methylation. Interestingly, SlALKBH2 has the ability to bind the transcript of SlDML2 , a DNA demethylase gene required for tomato fruit ripening, and modulates its stability via m 6 A demethylation. Mutation of SlALKBH2 decreases the abundance of SlDML2 mRNA and delays fruit ripening. Conclusions Our study identifies a novel layer of gene regulation for key ripening genes and establishes an essential molecular link between DNA methylation and mRNA m 6 A methylation during fruit ripening.

Background Epigenetic mark such as DNA methylation plays pivotal roles in regulating ripening of both climacteric and non-climacteric fruits. However, it remains unclear whether mRNA m 6 A methylation, which has been shown to regulate ripening of the tomato, a typical climacteric fruit, is functionally conserved for ripening control among different types of fruits. Results Here we show that m 6 A methylation displays a dramatic change at ripening onset of strawberry, a classical non-climacteric fruit. The m 6 A modification in coding sequence (CDS) regions appears to be ripening-specific and tends to stabilize the mRNAs, whereas m 6 A around the stop codons and within the 3′ untranslated regions is generally negatively correlated with the abundance of associated mRNAs. We identified thousands of transcripts with m 6 A hypermethylation in the CDS regions, including those of NCED5 , ABAR , and AREB1 in the abscisic acid (ABA) biosynthesis and signaling pathway. We demonstrate that the methyltransferases MTA and MTB are indispensable for normal ripening of strawberry fruit, and MTA-mediated m 6 A modification promotes mRNA stability of NCED5 and AREB1 , while facilitating translation of ABAR . Conclusion Our findings uncover that m 6 A methylation regulates ripening of the non-climacteric strawberry fruit by targeting the ABA pathway, which is distinct from that in the climacteric tomato fruit.

N6-methyladenosine (m 6 A) is the most abundant post-transcriptional modification in eukaryotic mRNA, extensively involved in RNA splicing, export, stability, and translation. In recent years, accumulating evidence has demonstrated that m 6 A modification plays a critical role in regulating the differentiation and function of immune cells. Among these, myeloid-derived suppressor cells (MDSCs), as a key immunosuppressive population within the tumor microenvironment (TME), accelerate tumor progression by inhibiting T cell activity and promoting immune evasion and therapy resistance. Emerging studies indicate that m 6 A modification modulates the development, accumulation, and immunosuppressive function of MDSCs, thereby contributing to tumor initiation and progression. This review provides a narrative overview of the current evidence regarding the crosstalk between m 6 A modification and MDSCs, with a focus on the underlying molecular mechanisms and their potential implications for cancer immunotherapy. Furthermore, we discuss future research directions and the challenges associated with clinical translation.

The epigenetic regulation of N6-methyladenosine (m 6 A) has attracted considerable interest in tumor research, but the potential roles of m 6 A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m 6 A regulators (including novel anti-readers) was employed to identify m 6 A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m 6 A regulator-related patterns were identified through the unsupervised clustering of 56 m 6 A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m 6 A-related scoring system was developed to quantify the m 6 A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m 6 A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m 6 A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.