Methylation of mRNAs, long noncoding RNAs, miRNAs, transfer RNAs and ribosomal RNAs have been termed “epitranscriptomics”. The most common RNA methylation is N6-methyladenosine (m6A), and other common RNA modifications include m1A, 5-methylcytosine (m5C), 1-methylguanosine (m1G), m2G, m6G and m7G. RNA methylation is regulated by RNA methyltransferases such as METTL3 and METTL14 (“writers”), RNA demethylases such as ALKBH5 and FTO (“erasers”), as well as RNA methylation site-binding proteins such as YTHDF1-3 and YTHDC1-2 (“readers”).RNA methylation and demethylation regulate gene transcription, pre-mRNA splicing, mRNA stability, protein translation, tumor initiation and progression. Small molecule compound inhibitors of RNA methyltransferases, demethylases and binding proteins have been discovered, and one of them is now in clinical trials in cancer patients.The first goal of this Research Topic is to better understand the roles of methylation/demethylation of different RNAs at various sites, RNA methyltransferases, demethylases and RNA methylation site-binding proteins in tumor initiation and progression. It is important to note that the same RNA modification can play diverse roles in cancer of different organ origins due to varying cellular context. Elucidating the cellular context determining oncogenic or tumor suppressive function is critical for developing therapies targeting RNA methylation/demethylation.The other major goal of this Research Topic is to discover small molecule compounds which suppress oncogenic RNA methyltransferase, demethylases and binding proteins, as well as proteolysis-targeting chimera (PROTAC) compounds which induce RNA modification protein degradation. While a small molecule compound METTL3 RNA methyltransferase inhibitor is already in clinical trials, RNA demethylase inhibitors currently available will not be proceeded into clinical trials. More research is required to develop more effective therapies targeting RNA methylation/demethylation.We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:• Mechanisms of RNA methylation and demethylation at different sites of RNAs, such as m6A, m1A, m5C, m1G, m2G, m6G , m7G and at different RNAs.• Mechanisms of RNA methylation and demethylation regulation by RNA methyltransferases, RNA demethylases and RNA methylation site-binding proteins.• The roles of diverse RNA methylation sites in RNA and protein expression and tumorigenesis.• The roles of varying RNA methyltransferases, demethylases and RNA methylation site-binding proteins in RNA and protein expression and tumorigenesis.• Cellular context determining differing effects of the same RNA methylation/demethylation on tumorigenesis.• Development of novel small molecule compound inhibitors of RNA methyltransferases, demethylases and binding proteins and demonstration of their anticancer efficacy.• Development of PROTAC degraders of RNA methyltransferases, demethylases and binding proteins and demonstration of their anticancer efficacy.• Clinical trials of RNA methylation/demethylation inhibitors in cancer patients.Please note manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic.
Methylation of mRNAs, long noncoding RNAs, miRNAs, transfer RNAs and ribosomal RNAs have been termed “epitranscriptomics”. The most common RNA methylation is N6-methyladenosine (m6A), and other common RNA modifications include m1A, 5-methylcytosine (m5C), 1-methylguanosine (m1G), m2G, m6G and m7G. RNA methylation is regulated by RNA methyltransferases such as METTL3 and METTL14 (“writers”), RNA demethylases such as ALKBH5 and FTO (“erasers”), as well as RNA methylation site-binding proteins such as YTHDF1-3 and YTHDC1-2 (“readers”).RNA methylation and demethylation regulate gene transcription, pre-mRNA splicing, mRNA stability, protein translation, tumor initiation and progression. Small molecule compound inhibitors of RNA methyltransferases, demethylases and binding proteins have been discovered, and one of them is now in clinical trials in cancer patients.The first goal of this Research Topic is to better understand the roles of methylation/demethylation of different RNAs at various sites, RNA methyltransferases, demethylases and RNA methylation site-binding proteins in tumor initiation and progression. It is important to note that the same RNA modification can play diverse roles in cancer of different organ origins due to varying cellular context. Elucidating the cellular context determining oncogenic or tumor suppressive function is critical for developing therapies targeting RNA methylation/demethylation.The other major goal of this Research Topic is to discover small molecule compounds which suppress oncogenic RNA methyltransferase, demethylases and binding proteins, as well as proteolysis-targeting chimera (PROTAC) compounds which induce RNA modification protein degradation. While a small molecule compound METTL3 RNA methyltransferase inhibitor is already in clinical trials, RNA demethylase inhibitors currently available will not be proceeded into clinical trials. More research is required to develop more effective therapies targeting RNA methylation/demethylation.We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:• Mechanisms of RNA methylation and demethylation at different sites of RNAs, such as m6A, m1A, m5C, m1G, m2G, m6G , m7G and at different RNAs.• Mechanisms of RNA methylation and demethylation regulation by RNA methyltransferases, RNA demethylases and RNA methylation site-binding proteins.• The roles of diverse RNA methylation sites in RNA and protein expression and tumorigenesis.• The roles of varying RNA methyltransferases, demethylases and RNA methylation site-binding proteins in RNA and protein expression and tumorigenesis.• Cellular context determining differing effects of the same RNA methylation/demethylation on tumorigenesis.• Development of novel small molecule compound inhibitors of RNA methyltransferases, demethylases and binding proteins and demonstration of their anticancer efficacy.• Development of PROTAC degraders of RNA methyltransferases, demethylases and binding proteins and demonstration of their anticancer efficacy.• Clinical trials of RNA methylation/demethylation inhibitors in cancer patients.Please note manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic.