Tomato(Solanum lycopersicum)is an extensively cultivated vegetable,and its growth and fruit quality can be significantly impaired by low temperatures.The widespread presence of N^(6)-methyladenosine(m^(6)A)modificatio...Tomato(Solanum lycopersicum)is an extensively cultivated vegetable,and its growth and fruit quality can be significantly impaired by low temperatures.The widespread presence of N^(6)-methyladenosine(m^(6)A)modification on RNA is involved in a diverse range of stress response processes.There is a significant knowledge gap regarding the precise roles of m^(6)A modification in tomato,particularly for cold stress response.Here,we assessed the m^(6)A modification landscape of S.lycopersicum'Micro-Tom'leaves in response to low-temperature stress.Furthermore,we investigated the potential relationship among m^(6)A modification,transcriptional regulation,alternative polyadenylation events,and protein translation via MeRIP-seq,RNA-seq,and protein mass spectrometry.After omic date analysis,11378 and 10735 significant m^(6)A peak associated genes were identified in the control and cold treatment tomato leaves,respectively.Additionally,we observed a UGUACAK(K=G/U)motif under both conditions.Differential m^(6)A site associated genes most likely play roles in protein translation regulatory pathway.Besides directly altering gene expression levels,m^(6)A also leads to differential poly(A)site usage under low-temperature.Finally,24 important candidate genes associated with cold stress were identified by system-level multi-omic analysis.Among them,m^(6)A modification levels were increased in SBPase(Sedoheptulose-1,7-bisphosphatase,Solyc05g052600.4)mRNA,causing distal poly(A)site usage,downregulation of mRNA expression level,and increased protein abundance.Through these,tomato leaves try to maintain normal photo synthetic carbon assimilation and nitro gen metabolism under low-temperature condition.The comprehensive investigation of the m^(6)A modification landscape and multi-omics analysis provide valuable insights into the epigenetic regulatory mechanisms in tomato cold stress response.展开更多
N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the transl...N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the translational efficiency of m^(6)A-modified mRNAs in the brain and is essential for learning and memory.However,its role in the mature retina remains unclear.Herein,we report a novel role of Ythdf1 in the maintenance of retinal function using a genetic knockout model.Loss of Ythdf1 resulted in impaired scotopic electroretinogram(ERG)responses and progressive retinal degeneration.Detailed analyses of rod photoreceptors confirmed substantial degenerative changes in the absence of ciliary defects.Single-cell RNA sequencing revealed comprehensive molecular alterations across all retinal cell types in Ythdf1-deficient retinas.Integrative analysis of methylated RNA immunoprecipitation(MeRIP)sequencing and RIP sequencing identified Tulp1 and Dhx38,two inheritable retinal degeneration disease-associated gene homologs,as direct targets of YTHDF1 in the retina.Specifically,YTHDF1 recognized and bound m^(6)A-modified Tulp1 and Dhx38 mRNA at the coding sequence(CDS),enhancing their translational efficiency without altering mRNA levels.Collectively,these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism of m^(6)A reader proteins in retinal degeneration,identifying potential therapeutic targets for severe retinopathies.展开更多
Ever since the first RNA nucleoside modification was charac- terized in 1957 [1], over 100 distinct chemical modifications have been identified in RNA to date [2]. Most of these modi- fications were characterized in n...Ever since the first RNA nucleoside modification was charac- terized in 1957 [1], over 100 distinct chemical modifications have been identified in RNA to date [2]. Most of these modi- fications were characterized in non-coding RNAs （ncRNAs）, including tRNA, rRNA, and small nuclear RNA （snRNA） [3]. Studies in the past few decades have located various mod- ifications in these ncRNAs and revealed their functional roles [3]. For instance, NLmethyladenosine （mlA）, which is typically found at position 58 in the tRNA T-loop of eukaryotes, func- tions to stabilize tRNA tertiary structure [4] and affect transla- tion by regulating the associations between tRNA and polysome [5]. Pseudouridine （tp） in snRNA can fine-tune branch site interactions and affect mRNA splicing [6].展开更多
We are very pleased to announce a special issue,to be published in the Spring of 2022,on"RNA Modifications and Epitranscriptomics"in the journal Genomics,Proteomics&Bioinformatics(GPB).More than 100 dist...We are very pleased to announce a special issue,to be published in the Spring of 2022,on"RNA Modifications and Epitranscriptomics"in the journal Genomics,Proteomics&Bioinformatics(GPB).More than 100 distinct chemical modifications to RNA have been characterized so far.They are prevalent in non-coding RNA,including rRNA,tRNA,and small nuclear RNA(snRNA).展开更多
The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNA...The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.展开更多
Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m^(6)A) modifi...Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m^(6)A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m^(6)A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m^(6)A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5′-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.展开更多
For a long time,mutations that do not alter protein sequences,so-called synonymous mutations,were largely overlooked.Scientists assumed they had little to no biological impact,considering them as neutral background no...For a long time,mutations that do not alter protein sequences,so-called synonymous mutations,were largely overlooked.Scientists assumed they had little to no biological impact,considering them as neutral background noise in the course of evolution.But a new study by Xin et al.(2025)challenges that assumption.Their research reveals that one such"silent"mutation played a pivotal role in cucumber domestication(Che and Zhang,2019).Rather than being inert,the mutation triggered a cascade of molecular changes involving mRNA structure and chemical modifications,ultimately altering hormone levels and growth patterns.These findings mark a turning point in our understanding of gene regulation,exposing RNA,not just DNA or protein,as a major driver of evolutionary change.展开更多
BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic comp...BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic complication,usually occurs at an earlier age and progresses faster than age-related cataracts.Evidence has linked N6-methyladenosine(m6A)to DC progression.However,there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis.AIM To elucidate the role played by altered m6A and differentially expressed mRNAs(DEmRNAs)in DC.METHODS Anterior lens capsules were collected from the control subjects and patients with DC.M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs.Through Gene Ontology and pathway enrichment(Kyoto Encyclopedia of Genes and Genomes)analyses,the potential role played by dysregulated m6A modification was predicted.Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases,demethylases,and readers.RESULTS Increased m6A abundance levels were found in the total mRNA of DC samples.Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs.The levels of five methylation-related genes-RBM15,WTAP,ALKBH5,FTO,and YTHDF1-were upregulated in DC samples.Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from DC patients.CONCLUSION M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway,rendering novel insights into therapeutic strategies for DC.展开更多
Epitranscriptomic chemical modifications of RNAs have emerged as potent regulatory mechanisms in the process of plant stress adaptation.Currently,over 170 distinct chemical modifications have been identified in mRNAs,...Epitranscriptomic chemical modifications of RNAs have emerged as potent regulatory mechanisms in the process of plant stress adaptation.Currently,over 170 distinct chemical modifications have been identified in mRNAs,tRNAs,rRNAs,microRNAs(miRNAs),and long noncoding RNAs(lncRNAs).Genetic and molec-ular studies have identified the genes responsible for addition and removal of chemical modifications from RNA molecules,which are known as"writers"and"erasers,"respectively.N^(6)-methyladenosine(m^(6)A)is the most prevalent chemical modification identified in eukaryotic mRNAs.Recent studies have identified m6 A writers and erasers across different plant species,including Arabidopsis(Arabidopsis thaliana),rice(Oryza sativa),cotton(Gossypium hirsutum),and tomato(Solanum lycopersicum).Accumulating discoveries have improved our understanding of the functions of RNA modifications in plant stress responses.This review highlights the latest research on RNA modification,emphasizing the biological and cellular roles of diverse chemical modifications of mRNAs,tRNAs,rRNAs,miRNAs,and lncRNAs in plant responses to environ-mental and hormonal signals.We also propose and discuss critical questions and future challenges for enhancing our understanding of the cellular and mechanistic roles of RNA modifications in plant stress re-sponses.Integrating molecular insights into the regulatory roles of RNA modifications in stress responses with novel genome-and RNA-editing technologies will facilitate the breeding of stress-tolerant crops through precise engineering of RNA modifications.展开更多
Male fertility is built on the proper proliferation and differentiation of germline cells within the seminiferous epithelium in the testis,which continuously produces millions of sperm per day in mammals[1].RNA modifi...Male fertility is built on the proper proliferation and differentiation of germline cells within the seminiferous epithelium in the testis,which continuously produces millions of sperm per day in mammals[1].RNA modifications are emerging as crucial epitranscriptomic regulators.展开更多
Proper ovarian follicle development,which is required for the maintenance of female fertility,is critical for the production of mature oocytes[1,2].Meanwhile,the correct establishment of the epitranscriptome in oocyte...Proper ovarian follicle development,which is required for the maintenance of female fertility,is critical for the production of mature oocytes[1,2].Meanwhile,the correct establishment of the epitranscriptome in oocytes is essential for precise gene repression and the acquisition of developmental competence[1–5].The ac4C modification is the third most abundant chemical modification in transcriptome[6,7].NAT10,the only known writer of ac4C,has been shown to participate in physiological and disease settings[6,8–11].However,NAT10-targeted transcripts in oocytes as well as their functions in supporting folliculogenesis are poorly understood.展开更多
Modifications to RNA have recently been recognized as a pivotal regulator of gene expression in living organisms.More than 170 chemical modifications have been identified in RNAs,with N6-methyladenosine(m^(6)A)being t...Modifications to RNA have recently been recognized as a pivotal regulator of gene expression in living organisms.More than 170 chemical modifications have been identified in RNAs,with N6-methyladenosine(m^(6)A)being the most abundant modification in eukaryotic mRNAs.The addition and removal of m^(6)A marks are catalyzed by methyltransferases(referred to as“writers”)and demethylases(referred to as“erasers”),respectively.In addition,the m^(6)A marks in mRNAs are recognized and interpreted by m^(6)A-binding proteins(referred to as“readers”),which regulate the fate of mRNAs,including stability,splicing,transport,and translation.Therefore,exploring the mechanism underlying the m^(6)A reader-mediated modulation of RNA metabolism is essential for a much deeper understanding of the epigenetic role of RNA modification in plants.Recent discoveries have improved our understanding of the functions of m^(6)A readers in plant growth and development,stress response,and disease resistance.This review highlights the latest developments in m^(6)A reader research,emphasizing the diverse RNA-binding domains crucial for m^(6)A reader function and the biological and cellular roles of m^(6)A readers in the plant response to developmental and environmental signals.Moreover,we propose and discuss the potential future research directions and challenges in identifying novel m^(6)A readers and elucidating the cellular and mechanistic role of m^(6)A readers in plants.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
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, s...Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine （m6A）, a mod- ification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes （methylase） and eraser （RNA demethylase） proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.展开更多
More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of ep...More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of epitranscriptomies. The m^6A modification is the most abundant modification in mRNA and non-coding RNA （ncRNA）. At the molecular level, m^6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA （miRNA） maturation, playing essential roles in a range of cellular processes. The m^6A modification is regulated by three classes of proteins generally referred to as the ＂writer＂ （adenosine methyltransferase）, ＂eraser＂ （m^6A demethylating enzyme）, and ＂reader＂ （m^6A-binding protein）. The m^6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology （YTH） family proteins, selectively bind to RNA and affect its fate in an m^6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m^6A modification, and provide our insights into the m^6A-mediated gene regulation.展开更多
The biological functions of the epitranscriptomic modification N^(6)-methyladenosine(m^(6)A)in plants are not fully understood.CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPS...The biological functions of the epitranscriptomic modification N^(6)-methyladenosine(m^(6)A)in plants are not fully understood.CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPSF30-S and an m^(6)A-binding YTH domain.Little is known about the biological roles of CPSF30-L and the molecular mechanism underlying its m^(6)A-binding function in alternative polyadenylation.Here,we charac-terized CPSF30-L as an Arabidopsis m^(6)A reader whose m^(6)A-binding function is required for the floral tran-sition and abscisic acid(ABA)response.We found that the m^(6)A-binding activity of CPSF30-L enhances the formation of liquid-like nuclear bodies,where CPSF30-L mainly recognizes m*A-modified far-upstream elements to control polyadenylation site choice.Deficiency of CPSF30-L lengthens the 3'untranslated region of three phenotypes-related transcripts,thereby accelerating their mRNA degradation and leading to late flowering and ABA hypersensitivity.Collectively,this study uncovers a new molecular mechanism for m^(6)A-driven phase separation and polyadenylation in plants.展开更多
Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abun...Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abundant and conserved epi-transcriptomic modification in eukaryotic cells,which has great impacts on RNA production and metabolism,including RNA splicing,processing,degradation and translation.Accumulating evidence demonstrates that m^(6)A plays a critical role in regulating cancer metastasis.However,there is a lack of studies that review the recent advances of m^(6)A in cancer metastasis.Here,we systematically retrieved the functions and mechanisms of how the m^(6)A axis regulates metastasis,and especially summarized the organ-specific liver,lung and brain metastasis mediated by m^(6)A in various cancers.Moreover,we discussed the potential application of m^(6)A modification in cancer diagnosis and therapy,as well as the present limitations and future perspectives of m^(6)A in cancer metastasis.This review provides a comprehensive knowledge on the m^(6)A-mediated regulation of gene expression,which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m^(6)A alteration.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
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
N6-Methyladenosine(m^(6)A)is the most abundant internal chemical modification in eukaryotic mRNA and plays important roles in gene expression regulation,including transcriptional and post-transcriptional regulation.m^...N6-Methyladenosine(m^(6)A)is the most abundant internal chemical modification in eukaryotic mRNA and plays important roles in gene expression regulation,including transcriptional and post-transcriptional regulation.m^(6)A is a reversible modification that is installed,removed,and recognized by methyltransferases(writers),demethylases(erasers),and m^(6)A-binding proteins(readers),respectively.Recently,the breadth of research on m^(6)A in plants has expanded,and the vital roles of m^(6)A in plant development,biotic and abiotic stress responses,and crop trait improvement have been investigated.In this review,we discuss recent developments in research on m^(6)A and highlight the detection methods,distribution,regulatory proteins,and molecular and biological functions of m^(6)A in plants.We also offer some perspectives on future investigations,providing direction for subsequent research on m^(6)A in plants.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant Nos.32202518 and 32070601)Shandong University of Technology PhD Start-up Fund(418097)。
文摘Tomato(Solanum lycopersicum)is an extensively cultivated vegetable,and its growth and fruit quality can be significantly impaired by low temperatures.The widespread presence of N^(6)-methyladenosine(m^(6)A)modification on RNA is involved in a diverse range of stress response processes.There is a significant knowledge gap regarding the precise roles of m^(6)A modification in tomato,particularly for cold stress response.Here,we assessed the m^(6)A modification landscape of S.lycopersicum'Micro-Tom'leaves in response to low-temperature stress.Furthermore,we investigated the potential relationship among m^(6)A modification,transcriptional regulation,alternative polyadenylation events,and protein translation via MeRIP-seq,RNA-seq,and protein mass spectrometry.After omic date analysis,11378 and 10735 significant m^(6)A peak associated genes were identified in the control and cold treatment tomato leaves,respectively.Additionally,we observed a UGUACAK(K=G/U)motif under both conditions.Differential m^(6)A site associated genes most likely play roles in protein translation regulatory pathway.Besides directly altering gene expression levels,m^(6)A also leads to differential poly(A)site usage under low-temperature.Finally,24 important candidate genes associated with cold stress were identified by system-level multi-omic analysis.Among them,m^(6)A modification levels were increased in SBPase(Sedoheptulose-1,7-bisphosphatase,Solyc05g052600.4)mRNA,causing distal poly(A)site usage,downregulation of mRNA expression level,and increased protein abundance.Through these,tomato leaves try to maintain normal photo synthetic carbon assimilation and nitro gen metabolism under low-temperature condition.The comprehensive investigation of the m^(6)A modification landscape and multi-omics analysis provide valuable insights into the epigenetic regulatory mechanisms in tomato cold stress response.
基金supported by the National Natural Science Foundation of China(82371083,82471100,82121003,82271084)Program of Science and Technology International Cooperation Project of Qinghai province(China)(2022-HZ-814)。
文摘N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the translational efficiency of m^(6)A-modified mRNAs in the brain and is essential for learning and memory.However,its role in the mature retina remains unclear.Herein,we report a novel role of Ythdf1 in the maintenance of retinal function using a genetic knockout model.Loss of Ythdf1 resulted in impaired scotopic electroretinogram(ERG)responses and progressive retinal degeneration.Detailed analyses of rod photoreceptors confirmed substantial degenerative changes in the absence of ciliary defects.Single-cell RNA sequencing revealed comprehensive molecular alterations across all retinal cell types in Ythdf1-deficient retinas.Integrative analysis of methylated RNA immunoprecipitation(MeRIP)sequencing and RIP sequencing identified Tulp1 and Dhx38,two inheritable retinal degeneration disease-associated gene homologs,as direct targets of YTHDF1 in the retina.Specifically,YTHDF1 recognized and bound m^(6)A-modified Tulp1 and Dhx38 mRNA at the coding sequence(CDS),enhancing their translational efficiency without altering mRNA levels.Collectively,these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism of m^(6)A reader proteins in retinal degeneration,identifying potential therapeutic targets for severe retinopathies.
基金supported by the National Key Research and Development Program from the Ministry of Science and Technology of China(Grant No.2016YFC0900300)the Beijing Natural Science Foundation(Grant No.5162012)of China awarded to CY
文摘Ever since the first RNA nucleoside modification was charac- terized in 1957 [1], over 100 distinct chemical modifications have been identified in RNA to date [2]. Most of these modi- fications were characterized in non-coding RNAs （ncRNAs）, including tRNA, rRNA, and small nuclear RNA （snRNA） [3]. Studies in the past few decades have located various mod- ifications in these ncRNAs and revealed their functional roles [3]. For instance, NLmethyladenosine （mlA）, which is typically found at position 58 in the tRNA T-loop of eukaryotes, func- tions to stabilize tRNA tertiary structure [4] and affect transla- tion by regulating the associations between tRNA and polysome [5]. Pseudouridine （tp） in snRNA can fine-tune branch site interactions and affect mRNA splicing [6].
文摘We are very pleased to announce a special issue,to be published in the Spring of 2022,on"RNA Modifications and Epitranscriptomics"in the journal Genomics,Proteomics&Bioinformatics(GPB).More than 100 distinct chemical modifications to RNA have been characterized so far.They are prevalent in non-coding RNA,including rRNA,tRNA,and small nuclear RNA(snRNA).
基金funded by Notingham University and the Neuroscience Support Group Charity,UK(to HMK)supported by a CONACYT PhD scholarshipMD?was supported by the Postdoctoral Research Fellowship Program of TUBITAK。
文摘The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.
基金supported by the National Natural Science Foundation of China(81970841,82101160,82121003)the Department of Science and Technology of Sichuan Province(2023ZYD0172,2023YFS0161)+3 种基金the program of Science and Technology International Cooperation Project of Qinghai province(China)(No.2022-HZ-814)Sichuan Intellectual Property Office(China)(No.2022-ZS-0070)the CAMS Innovation Fund for Medical Sciences(2019-12M-5-032)Open Project of Henan Provincial Key Laboratory of Ophthalmology and Visual Science(20KFKT02).
文摘Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m^(6)A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m^(6)A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m^(6)A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5′-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.
基金A.Bendahmane and A.Boualem are supported by Saclay Plant Sciences(SPS)(ANR-17-EUR-0007)the NectarGland ERC Project(101095736)+1 种基金Explor'ae ANR-24-RRll-0003the Plant Biology and Breeding Department of INRAE.
文摘For a long time,mutations that do not alter protein sequences,so-called synonymous mutations,were largely overlooked.Scientists assumed they had little to no biological impact,considering them as neutral background noise in the course of evolution.But a new study by Xin et al.(2025)challenges that assumption.Their research reveals that one such"silent"mutation played a pivotal role in cucumber domestication(Che and Zhang,2019).Rather than being inert,the mutation triggered a cascade of molecular changes involving mRNA structure and chemical modifications,ultimately altering hormone levels and growth patterns.These findings mark a turning point in our understanding of gene regulation,exposing RNA,not just DNA or protein,as a major driver of evolutionary change.
基金Supported by the National Natural Science Foundation of China,No.82171039.
文摘BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic complication,usually occurs at an earlier age and progresses faster than age-related cataracts.Evidence has linked N6-methyladenosine(m6A)to DC progression.However,there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis.AIM To elucidate the role played by altered m6A and differentially expressed mRNAs(DEmRNAs)in DC.METHODS Anterior lens capsules were collected from the control subjects and patients with DC.M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs.Through Gene Ontology and pathway enrichment(Kyoto Encyclopedia of Genes and Genomes)analyses,the potential role played by dysregulated m6A modification was predicted.Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases,demethylases,and readers.RESULTS Increased m6A abundance levels were found in the total mRNA of DC samples.Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs.The levels of five methylation-related genes-RBM15,WTAP,ALKBH5,FTO,and YTHDF1-were upregulated in DC samples.Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from DC patients.CONCLUSION M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway,rendering novel insights into therapeutic strategies for DC.
基金supported by the Mid-Career Researcher Program through the National Research Foundation of Korea funded by the Ministry of Science,ICT,and Future Planning(NRF-2021R1A2C1004187)Republic of Korea+3 种基金the Qing Lan Project of Jiangsu Province(2024)the Natural Science Foundation of Jiangsu Province(grant NoBK20241054)the Program of the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(23KJB550004)the High-Level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China(JSSCBS20230419).
文摘Epitranscriptomic chemical modifications of RNAs have emerged as potent regulatory mechanisms in the process of plant stress adaptation.Currently,over 170 distinct chemical modifications have been identified in mRNAs,tRNAs,rRNAs,microRNAs(miRNAs),and long noncoding RNAs(lncRNAs).Genetic and molec-ular studies have identified the genes responsible for addition and removal of chemical modifications from RNA molecules,which are known as"writers"and"erasers,"respectively.N^(6)-methyladenosine(m^(6)A)is the most prevalent chemical modification identified in eukaryotic mRNAs.Recent studies have identified m6 A writers and erasers across different plant species,including Arabidopsis(Arabidopsis thaliana),rice(Oryza sativa),cotton(Gossypium hirsutum),and tomato(Solanum lycopersicum).Accumulating discoveries have improved our understanding of the functions of RNA modifications in plant stress responses.This review highlights the latest research on RNA modification,emphasizing the biological and cellular roles of diverse chemical modifications of mRNAs,tRNAs,rRNAs,miRNAs,and lncRNAs in plant responses to environ-mental and hormonal signals.We also propose and discuss critical questions and future challenges for enhancing our understanding of the cellular and mechanistic roles of RNA modifications in plant stress re-sponses.Integrating molecular insights into the regulatory roles of RNA modifications in stress responses with novel genome-and RNA-editing technologies will facilitate the breeding of stress-tolerant crops through precise engineering of RNA modifications.
基金supported by the National Key Research and Development Program ofChina(2019YFA0802600,2022YFC2702600)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM"(QYPY20230032)+4 种基金the National Natural Science Foundation of China(31970793,32170856 and 32300711)the Anhui Provincial Natural Science Foundation grant(2408085jJ016)the Reproductive and Genetic Hospital of CITIC-XIANGYA(YNXM-202211)the Hunan Provincial Grant for Innovative Province Construction(2019SK4012)the Hundred Youth Talents Program of Hunan Province.
文摘Male fertility is built on the proper proliferation and differentiation of germline cells within the seminiferous epithelium in the testis,which continuously produces millions of sperm per day in mammals[1].RNA modifications are emerging as crucial epitranscriptomic regulators.
基金supported by the National Key Research and Development Program of China(2021YFC2700100)the Natural Science Foundation of Zhejiang Province(LD22C060001)+2 种基金the National Natural Science Foundation of China(31930031)the fellowship of China National Postdoctoral Program for Innovative Talents(BX20230031)Beijing Natural Science Foundation(7244435).
文摘Proper ovarian follicle development,which is required for the maintenance of female fertility,is critical for the production of mature oocytes[1,2].Meanwhile,the correct establishment of the epitranscriptome in oocytes is essential for precise gene repression and the acquisition of developmental competence[1–5].The ac4C modification is the third most abundant chemical modification in transcriptome[6,7].NAT10,the only known writer of ac4C,has been shown to participate in physiological and disease settings[6,8–11].However,NAT10-targeted transcripts in oocytes as well as their functions in supporting folliculogenesis are poorly understood.
基金supported by a grant from the Mid-Career Re-searcher Program through the National Research Foundation of Korea funded by the Ministry of Science,ICT and Future Planning(NRF-2021R1A2C1004187),Republic of Korea.
文摘Modifications to RNA have recently been recognized as a pivotal regulator of gene expression in living organisms.More than 170 chemical modifications have been identified in RNAs,with N6-methyladenosine(m^(6)A)being the most abundant modification in eukaryotic mRNAs.The addition and removal of m^(6)A marks are catalyzed by methyltransferases(referred to as“writers”)and demethylases(referred to as“erasers”),respectively.In addition,the m^(6)A marks in mRNAs are recognized and interpreted by m^(6)A-binding proteins(referred to as“readers”),which regulate the fate of mRNAs,including stability,splicing,transport,and translation.Therefore,exploring the mechanism underlying the m^(6)A reader-mediated modulation of RNA metabolism is essential for a much deeper understanding of the epigenetic role of RNA modification in plants.Recent discoveries have improved our understanding of the functions of m^(6)A readers in plant growth and development,stress response,and disease resistance.This review highlights the latest developments in m^(6)A reader research,emphasizing the diverse RNA-binding domains crucial for m^(6)A reader function and the biological and cellular roles of m^(6)A readers in the plant response to developmental and environmental signals.Moreover,we propose and discuss the potential future research directions and challenges in identifying novel m^(6)A readers and elucidating the cellular and mechanistic role of m^(6)A readers in plants.
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supported by the Intramural Research Program of the NIH,National Cancer Institute,Center for Cancer Research,United States of America
文摘Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine （m6A）, a mod- ification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes （methylase） and eraser （RNA demethylase） proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.
基金supported by the National Natural Science Foundation of China(Grant No.31722017)
文摘More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of epitranscriptomies. The m^6A modification is the most abundant modification in mRNA and non-coding RNA （ncRNA）. At the molecular level, m^6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA （miRNA） maturation, playing essential roles in a range of cellular processes. The m^6A modification is regulated by three classes of proteins generally referred to as the ＂writer＂ （adenosine methyltransferase）, ＂eraser＂ （m^6A demethylating enzyme）, and ＂reader＂ （m^6A-binding protein）. The m^6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology （YTH） family proteins, selectively bind to RNA and affect its fate in an m^6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m^6A modification, and provide our insights into the m^6A-mediated gene regulation.
基金This work was supported by the National Natural Science Foundation of China(nos.21822702,21820102008,92053109,and 21432002)the National Basic Research Program of China(2017YFA0505201 and 2019YFA0802201).
文摘The biological functions of the epitranscriptomic modification N^(6)-methyladenosine(m^(6)A)in plants are not fully understood.CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPSF30-S and an m^(6)A-binding YTH domain.Little is known about the biological roles of CPSF30-L and the molecular mechanism underlying its m^(6)A-binding function in alternative polyadenylation.Here,we charac-terized CPSF30-L as an Arabidopsis m^(6)A reader whose m^(6)A-binding function is required for the floral tran-sition and abscisic acid(ABA)response.We found that the m^(6)A-binding activity of CPSF30-L enhances the formation of liquid-like nuclear bodies,where CPSF30-L mainly recognizes m*A-modified far-upstream elements to control polyadenylation site choice.Deficiency of CPSF30-L lengthens the 3'untranslated region of three phenotypes-related transcripts,thereby accelerating their mRNA degradation and leading to late flowering and ABA hypersensitivity.Collectively,this study uncovers a new molecular mechanism for m^(6)A-driven phase separation and polyadenylation in plants.
基金supported by the Key Program of the National Natural Science Foundation of China(81930074,2020-2024)the Major Program of National Natural Science Foundation of China(91959203,2020-2023)the Natural Science Foundation of China(81672820,2017-2020,81672378,2017-2020,82173093)。
文摘Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abundant and conserved epi-transcriptomic modification in eukaryotic cells,which has great impacts on RNA production and metabolism,including RNA splicing,processing,degradation and translation.Accumulating evidence demonstrates that m^(6)A plays a critical role in regulating cancer metastasis.However,there is a lack of studies that review the recent advances of m^(6)A in cancer metastasis.Here,we systematically retrieved the functions and mechanisms of how the m^(6)A axis regulates metastasis,and especially summarized the organ-specific liver,lung and brain metastasis mediated by m^(6)A in various cancers.Moreover,we discussed the potential application of m^(6)A modification in cancer diagnosis and therapy,as well as the present limitations and future perspectives of m^(6)A in cancer metastasis.This review provides a comprehensive knowledge on the m^(6)A-mediated regulation of gene expression,which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m^(6)A alteration.
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.
基金supported by the National Natural Science Foundation of China(22225704,21820102008,92053109)the National Basic Research Program of China(2019YFA0802201)the Beijing Natural Science Foundation(Z200010).
文摘N6-Methyladenosine(m^(6)A)is the most abundant internal chemical modification in eukaryotic mRNA and plays important roles in gene expression regulation,including transcriptional and post-transcriptional regulation.m^(6)A is a reversible modification that is installed,removed,and recognized by methyltransferases(writers),demethylases(erasers),and m^(6)A-binding proteins(readers),respectively.Recently,the breadth of research on m^(6)A in plants has expanded,and the vital roles of m^(6)A in plant development,biotic and abiotic stress responses,and crop trait improvement have been investigated.In this review,we discuss recent developments in research on m^(6)A and highlight the detection methods,distribution,regulatory proteins,and molecular and biological functions of m^(6)A in plants.We also offer some perspectives on future investigations,providing direction for subsequent research on m^(6)A in plants.
