Altered metabolism is a hallmark of cancer,and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors.It is well recognized that long noncoding RNAs(lncRNAs)regulate ene...Altered metabolism is a hallmark of cancer,and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors.It is well recognized that long noncoding RNAs(lncRNAs)regulate energy metabolism in cancer.However,lncRNA-mediated posttranslational modifications and metabolic reprogramming are unclear at present.In this review,we summarized the current understanding of the interactions between the alterations in cancer-associated energy metabolism and the lncRNA-mediated posttranslational modifications of metabolic enzymes,transcription factors,and other proteins involved in metabolic pathways.In addition,we discuss the mechanisms through which these interactions contribute to tumor initiation and progression,and the key roles and clinical significance of functional lncRNAs.We believe that an in-depth understanding of lncRNA-mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.展开更多
Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many importan...Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N^6-methyladenosine (m^6A) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, m^6A can be incorporated by a methyltransferase complex and removed by demethy- lases, which ensures that the m^6A modification is reversible and dynamic. Moreover, m^6A is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m^6A recognition by YTH domaincontaining proteins, which would shed new light on m^6A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.展开更多
Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy.If the etiology cannot be eliminated,liver fibrosis progresses to cirrhosis and eventually to liver failure or malignanc...Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy.If the etiology cannot be eliminated,liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy;both are associated with a fatal outcome.Liver transplantation,the only curative therapy,is still mostly unavailable.Liver fibrosis was shown to be a reversible process;however,complete reversibility remains debatable.Recently,the molecular markers of liver fibrosis were shown to be transmitted across generations.Epigenetic mechanisms including DNA methylation,histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis.Furthermore,epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations.However,the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated.This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers.The fact that epigenetic changes,unlike genetic mutations,are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis,to prevent the development of malignancy and to regulate heritability of fibrosis phenotype.展开更多
Over 17 and 160 types of chemical modifications have been identified in DNA and RNA,respectively.The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edge...Over 17 and 160 types of chemical modifications have been identified in DNA and RNA,respectively.The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics.Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study.Here,we review the recent technological advances in this rapidly evolving field.We focus on high-throughput detection methods and biological findings for these modifications,and discuss questions to be addressed as well.We also summarize third-generation sequencing methods,which enable long-read and single-molecule sequencing of DNA and RNA modification.展开更多
N^6-methyladenosine (m^6A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism, m^6A modification could be installed by m^6A "writ...N^6-methyladenosine (m^6A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism, m^6A modification could be installed by m^6A "writers" composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m^6A "erasers" (FTO and ALKBH5). The function of m^6A is executed by m^6A "readers" that bind to m^6A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in m^6A modulators ("writers," "erasers," and "readers") have remarkably renewed our understanding of the function and regulation of m^6A in different cells under normal or disease conditions. However, the mechanism and the regulatory network of m^6A are still largely unknown. Moreover, investigations of the m^6A physiological roles in human diseases are limited. In this review, we summarize the recent advances in m^6A research and highlight the functional relevance and importance of m^6A modification in in vitro cell lines, in physiological contexts, and in cancers.展开更多
N^6-methyladenosine(m^6 A) is an essential RNA modification that regulates key cellular processes, including stem cell renewal,cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant m^6 A methy...N^6-methyladenosine(m^6 A) is an essential RNA modification that regulates key cellular processes, including stem cell renewal,cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant m^6 A methylation has been implicated in the development and maintenance of diverse human cancers. Altered m^6 A levels affect RNA processing, mRNA degradation, and translation of mRNAs into proteins, thereby disrupting gene expression regulation and promoting tumorigenesis. Recent studies have reported that the abnormal expression of m^6 A regulatory enzymes affects m^6 A abundance and consequently dysregulates the expression of tumor suppressor genes and oncogenes, including MYC, SOCS2, ADAM19, and PTEN. In this review, we discuss the specific roles of m^6 A missing space "writers", "erasers", and "readers" in normal physiology and how their altered expression promotes tumorigenesis. We also describe the potential of exploiting the aberrant expression of these enzymes for cancer diagnosis, prognosis, and the development of novel therapies.展开更多
N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previo...N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previously determined.However,the MTDs alone possess no enzymatic activity.Here we present the solution structure for the zinc finger domain(ZFD)of METTL3,the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14.We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3'consensus sequence,but does not to one without.The ZFD thus serves as the target recognition domain,a structural feature previously shown for DNA methyltransferases,and cooperates with the MTDs of METTL3-METTL14 for catalysis.However,the interaction between the ZFD and the specific RNA is extremely weak,with the binding affinity at several hundred micromolar under physiological conditions.The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel P-sheet.Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface.As a division of labor,the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues fromβ-sheet and zinc finger 2.Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded,which may permit the cooperation between the two domains during catalysis.Together,the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification.展开更多
Advances in the detection and mapping of messenger RNA(mRNA)N^6-methyladenosine(m 6A)and 5-methylcytosine(m 5C),and DNA N^6-methyldeoxyadenosine(6mA)redefined our understanding of these modifications as additional tie...Advances in the detection and mapping of messenger RNA(mRNA)N^6-methyladenosine(m 6A)and 5-methylcytosine(m 5C),and DNA N^6-methyldeoxyadenosine(6mA)redefined our understanding of these modifications as additional tiers of epigenetic regulation.In plants,the most prevalent internal mRNA modifications,m^6A and m^5C,play crucial and dynamic roles in many processes,including embryo development,stem cell fate determination,trichome branching,leaf morphogenesis,floral transition,stress responses,fruit ripening,and root development.The newly identified and widespread epigenetic marker 6mA DNA methylation is associated with gene expression,plant development,and stress responses.Here,we review the latest research progress on mRNA and DNA epigenetic modifications,including the detection,dynamics,distribution,functions,regulatory proteins,and evolution,with a focus on m^6A,m^5C,and 6mA.We also provide some perspectives on future research of the newly identified and unknown epigenetic modifications of mRNA and DNA in plants.展开更多
Deposition of the histone variant H2A.Z at gene bodies regulates transcription by modifying chromatin accessibility in plants. However, the role of H2A.Z enrichment at the promoter and enhancer regions is unclear, and...Deposition of the histone variant H2A.Z at gene bodies regulates transcription by modifying chromatin accessibility in plants. However, the role of H2A.Z enrichment at the promoter and enhancer regions is unclear, and how H2A.Z interacts with other mechanisms of chromatin modification to regulate gene expression remains obscure. Here, we mapped genome-wide H2A.Z, H3K4me3, H3K27me3, Pol II, and nucleosome occupancy in Arabidopsis inflorescence. We showed that H2A.Z preferentially associated with H3K4me3 at promoters, while it was found with H3K27me3 at enhancers, and that H2A.Z deposition negatively correlated with gene expression. In addition, we demonstrated that H2A.Z represses gene expression by establishing low gene accessibility at +1 nucleosome and maintaining high gene accessibility at -1 nucleosome. We further showed that the high measures of gene responsiveness correlate with the H2A.Z-associated closed +1 nucleosome structure. Moreover, we found that H2A.Z represses enhancer activity by promoting H3K27me3 and preventing H3K4me3 histone modifications. This study provides a framework for future studies of H2A.Z functions and opens up new aspects for decoding the interplay between chromatin modification and histone variants in transcrip- tional control.展开更多
As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings ...As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.展开更多
More than 100 modifications have been found in RNA. Analogous to epigenetic DNA methylation, epitranscriptomic modifications can be written, read, and erased by a complex network of proteins. Apart from Na-methyladeno...More than 100 modifications have been found in RNA. Analogous to epigenetic DNA methylation, epitranscriptomic modifications can be written, read, and erased by a complex network of proteins. Apart from Na-methyladenosine (m6A), N1-methyladenosine (mXA) has been found as a reversible modification in tRNA and mRNA. mlA occurs at positions 9, 14, and 58 of tRNA, with m1A58 being critical for tRNA stability. Other than the hundreds of m1A sites in mRNA and long non-coding RNA transcripts, transcriptome-wide mapping of m1A also identifies 〉 20 m1A sites in mitochondrial genes, m1A in the coding region of mitochondrial transcripts can inhibit the translation of the corresponding proteins. In this review, we summarize the current understanding of mlA in mRNA and tRNA, covering high-throughput sequencing methods developed for m1A methylome, m1A-related enzymes (writers and erasers), as well as its functions in mRNA and tRNA.展开更多
基金This study was supported by the National Key R&D Program of China(2018YFC1313304 and 2018YFC1313300)the National Natural Science Foundation of China(82073112,82022052 and 81871951).
文摘Altered metabolism is a hallmark of cancer,and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors.It is well recognized that long noncoding RNAs(lncRNAs)regulate energy metabolism in cancer.However,lncRNA-mediated posttranslational modifications and metabolic reprogramming are unclear at present.In this review,we summarized the current understanding of the interactions between the alterations in cancer-associated energy metabolism and the lncRNA-mediated posttranslational modifications of metabolic enzymes,transcription factors,and other proteins involved in metabolic pathways.In addition,we discuss the mechanisms through which these interactions contribute to tumor initiation and progression,and the key roles and clinical significance of functional lncRNAs.We believe that an in-depth understanding of lncRNA-mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.
基金supported by the National Natural Science Foundation of China awarded to SL(Grant No.31500601)and CX(Grants Nos.31570737 and 31770806)supported by the“1000 Young Talents Program”of China
文摘Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N^6-methyladenosine (m^6A) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, m^6A can be incorporated by a methyltransferase complex and removed by demethy- lases, which ensures that the m^6A modification is reversible and dynamic. Moreover, m^6A is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m^6A recognition by YTH domaincontaining proteins, which would shed new light on m^6A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.
基金Egyptian Science and Technology Development Fund under Project 1550
文摘Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy.If the etiology cannot be eliminated,liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy;both are associated with a fatal outcome.Liver transplantation,the only curative therapy,is still mostly unavailable.Liver fibrosis was shown to be a reversible process;however,complete reversibility remains debatable.Recently,the molecular markers of liver fibrosis were shown to be transmitted across generations.Epigenetic mechanisms including DNA methylation,histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis.Furthermore,epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations.However,the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated.This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers.The fact that epigenetic changes,unlike genetic mutations,are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis,to prevent the development of malignancy and to regulate heritability of fibrosis phenotype.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31861143026 to C.Y.)the Ministry of Science and Technology of China(Grant Nos.2019YFA0110902 and 2019YFA08002501 to C.Y.)the Ludwig Institute for Cancer Research(C-X.S.),Cancer Research UK(C63763/A26394 and C63763/A27122 to C-X.S.)NIHR Oxford Biomedical Research Centre(to C-X.S.)and Emerson Collective(to C-X.S.).L-Y.Z.is supported by China Scholarship Council.The views expressed are those of the authors and not necessarily those of the NHS,the NIHR or the Department of Health.We apologize for not being able to cite all the publications related to this topic due to space constraints of the journal.
文摘Over 17 and 160 types of chemical modifications have been identified in DNA and RNA,respectively.The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics.Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study.Here,we review the recent technological advances in this rapidly evolving field.We focus on high-throughput detection methods and biological findings for these modifications,and discuss questions to be addressed as well.We also summarize third-generation sequencing methods,which enable long-read and single-molecule sequencing of DNA and RNA modification.
基金This work was supported by the National Natural Science Foundation of China (No. 91753141 to Hua-Bing Li).
文摘N^6-methyladenosine (m^6A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism, m^6A modification could be installed by m^6A "writers" composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m^6A "erasers" (FTO and ALKBH5). The function of m^6A is executed by m^6A "readers" that bind to m^6A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in m^6A modulators ("writers," "erasers," and "readers") have remarkably renewed our understanding of the function and regulation of m^6A in different cells under normal or disease conditions. However, the mechanism and the regulatory network of m^6A are still largely unknown. Moreover, investigations of the m^6A physiological roles in human diseases are limited. In this review, we summarize the recent advances in m^6A research and highlight the functional relevance and importance of m^6A modification in in vitro cell lines, in physiological contexts, and in cancers.
基金Justin Jong-Leong Wong holds a Fellowship from the Cancer Institute of NSW and receives funding from the National Health and Medical Research Council of Australia (Grant No 1128175, 1129901 and 1126306)
文摘N^6-methyladenosine(m^6 A) is an essential RNA modification that regulates key cellular processes, including stem cell renewal,cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant m^6 A methylation has been implicated in the development and maintenance of diverse human cancers. Altered m^6 A levels affect RNA processing, mRNA degradation, and translation of mRNAs into proteins, thereby disrupting gene expression regulation and promoting tumorigenesis. Recent studies have reported that the abnormal expression of m^6 A regulatory enzymes affects m^6 A abundance and consequently dysregulates the expression of tumor suppressor genes and oncogenes, including MYC, SOCS2, ADAM19, and PTEN. In this review, we discuss the specific roles of m^6 A missing space "writers", "erasers", and "readers" in normal physiology and how their altered expression promotes tumorigenesis. We also describe the potential of exploiting the aberrant expression of these enzymes for cancer diagnosis, prognosis, and the development of novel therapies.
文摘N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previously determined.However,the MTDs alone possess no enzymatic activity.Here we present the solution structure for the zinc finger domain(ZFD)of METTL3,the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14.We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3'consensus sequence,but does not to one without.The ZFD thus serves as the target recognition domain,a structural feature previously shown for DNA methyltransferases,and cooperates with the MTDs of METTL3-METTL14 for catalysis.However,the interaction between the ZFD and the specific RNA is extremely weak,with the binding affinity at several hundred micromolar under physiological conditions.The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel P-sheet.Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface.As a division of labor,the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues fromβ-sheet and zinc finger 2.Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded,which may permit the cooperation between the two domains during catalysis.Together,the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification.
基金This work was supported by funding from the National Transgenic Major Program of China(2019ZX08010-002)to X.G.the National Natural Sci ence Foundation of China(31871606,31671670)toX.G.,and the Recruit ment Program of Global Youth Expert of China to X.G.
文摘Advances in the detection and mapping of messenger RNA(mRNA)N^6-methyladenosine(m 6A)and 5-methylcytosine(m 5C),and DNA N^6-methyldeoxyadenosine(6mA)redefined our understanding of these modifications as additional tiers of epigenetic regulation.In plants,the most prevalent internal mRNA modifications,m^6A and m^5C,play crucial and dynamic roles in many processes,including embryo development,stem cell fate determination,trichome branching,leaf morphogenesis,floral transition,stress responses,fruit ripening,and root development.The newly identified and widespread epigenetic marker 6mA DNA methylation is associated with gene expression,plant development,and stress responses.Here,we review the latest research progress on mRNA and DNA epigenetic modifications,including the detection,dynamics,distribution,functions,regulatory proteins,and evolution,with a focus on m^6A,m^5C,and 6mA.We also provide some perspectives on future research of the newly identified and unknown epigenetic modifications of mRNA and DNA in plants.
文摘Deposition of the histone variant H2A.Z at gene bodies regulates transcription by modifying chromatin accessibility in plants. However, the role of H2A.Z enrichment at the promoter and enhancer regions is unclear, and how H2A.Z interacts with other mechanisms of chromatin modification to regulate gene expression remains obscure. Here, we mapped genome-wide H2A.Z, H3K4me3, H3K27me3, Pol II, and nucleosome occupancy in Arabidopsis inflorescence. We showed that H2A.Z preferentially associated with H3K4me3 at promoters, while it was found with H3K27me3 at enhancers, and that H2A.Z deposition negatively correlated with gene expression. In addition, we demonstrated that H2A.Z represses gene expression by establishing low gene accessibility at +1 nucleosome and maintaining high gene accessibility at -1 nucleosome. We further showed that the high measures of gene responsiveness correlate with the H2A.Z-associated closed +1 nucleosome structure. Moreover, we found that H2A.Z represses enhancer activity by promoting H3K27me3 and preventing H3K4me3 histone modifications. This study provides a framework for future studies of H2A.Z functions and opens up new aspects for decoding the interplay between chromatin modification and histone variants in transcrip- tional control.
文摘As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.
基金supported by the National Basic Research Program of China (Grant Nos. 2016YFC0900302 and 2017YFA0505201)the National Natural Science Foundation of China (Grant No. 21432002)
文摘More than 100 modifications have been found in RNA. Analogous to epigenetic DNA methylation, epitranscriptomic modifications can be written, read, and erased by a complex network of proteins. Apart from Na-methyladenosine (m6A), N1-methyladenosine (mXA) has been found as a reversible modification in tRNA and mRNA. mlA occurs at positions 9, 14, and 58 of tRNA, with m1A58 being critical for tRNA stability. Other than the hundreds of m1A sites in mRNA and long non-coding RNA transcripts, transcriptome-wide mapping of m1A also identifies 〉 20 m1A sites in mitochondrial genes, m1A in the coding region of mitochondrial transcripts can inhibit the translation of the corresponding proteins. In this review, we summarize the current understanding of mlA in mRNA and tRNA, covering high-throughput sequencing methods developed for m1A methylome, m1A-related enzymes (writers and erasers), as well as its functions in mRNA and tRNA.