N6-methyladenosine(m6A)is the most abundant inner RNA modification in eukaryotes.Due to the development of RNA sequencing technology,the distribution pattern of m6A in the transcriptome has been uncovered.Dynamically,...N6-methyladenosine(m6A)is the most abundant inner RNA modification in eukaryotes.Due to the development of RNA sequencing technology,the distribution pattern of m6A in the transcriptome has been uncovered.Dynamically,the reversible N6-methylation is mediated by two types of proteins,which are classified as“writers”and“erasers”.Under the association of specific co-factors,writers show spatiotemporal N6-methyltransferase activity.Mechanically,m6A can be recognized by“reader”proteins or can directly modify RNA conformation,and it widely affects gene expression by mediating RNA stability,translation,splicing and export.m6A is involved in a series of physiology processes.Dysregulation of m6A is gradually defined as the pathogenesis of some diseases,e.g.,cancer and cardiovascular disease.Therefore,a good understanding of m6A is essential for molecular biology and pathology research.In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators.The discovered biological and pathological processes affected by m6A are also summarized.We hope that readers with related research interests benefit from our review.展开更多
The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only so...The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m^6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m^6A modification （m^6Afreq genes） and those occasionally regulated by m^6A modification （m^6Aocca genes）. Compared to the m^6Aocca genes, the m^6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m^6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m^6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m^6A epitranscriptomic regulation and other gene expression regulatory machineries.展开更多
基金This work was supported by Taishan Scholar Program of Shandong Province(tsqn201812044)Natural Science Foundation of Shandong Province(JQ201815)National Natural Science Foundation of China(81900259).
文摘N6-methyladenosine(m6A)is the most abundant inner RNA modification in eukaryotes.Due to the development of RNA sequencing technology,the distribution pattern of m6A in the transcriptome has been uncovered.Dynamically,the reversible N6-methylation is mediated by two types of proteins,which are classified as“writers”and“erasers”.Under the association of specific co-factors,writers show spatiotemporal N6-methyltransferase activity.Mechanically,m6A can be recognized by“reader”proteins or can directly modify RNA conformation,and it widely affects gene expression by mediating RNA stability,translation,splicing and export.m6A is involved in a series of physiology processes.Dysregulation of m6A is gradually defined as the pathogenesis of some diseases,e.g.,cancer and cardiovascular disease.Therefore,a good understanding of m6A is essential for molecular biology and pathology research.In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators.The discovered biological and pathological processes affected by m6A are also summarized.We hope that readers with related research interests benefit from our review.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81670462 and 81422006 to QC)China Postdoctoral Science Foundation (Grant No. 2016M591024 to YZ)
文摘The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m^6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m^6A modification （m^6Afreq genes） and those occasionally regulated by m^6A modification （m^6Aocca genes）. Compared to the m^6Aocca genes, the m^6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m^6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m^6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m^6A epitranscriptomic regulation and other gene expression regulatory machineries.
