Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-met...Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
N6-methyladenosine(m^(6)A)is a dynamic and reversible epigenetic regulation.As the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression throu...N6-methyladenosine(m^(6)A)is a dynamic and reversible epigenetic regulation.As the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression through various mechanisms,such as mRNA splicing,nuclear export,localization,translation efficiency,mRNA stability,and structural transformation.The involvement of m^(6)A in the regulation of gene expression depends on the specific recognition of m^(6)A-modified RNA by reader proteins.In the pathogenesis and treatment of liver disease,studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m^(6)A modification,in which abnormal expression of reader proteins determines the fate of these gene transcripts.In this review,we introduce m^(6)A readers,summarize the recognition and regulatory mechanisms of m^(6)A readers on mRNA,and focus on the biological functions and mechanisms of m^(6)A readers in liver cancer,viral hepatitis,non-alcoholic fatty liver disease(NAFLD),hepatic fibrosis(HF),acute liver injury(ALI),and other liver diseases.This information is expected to be of high value to researchers deciphering the links between m^(6)A readers and human liver diseases.展开更多
N6-Methyladenosine(m^(6)A)is one of the most abundant modifications of eukaryotic mRNA,but its comprehensive biological functionality remains further exploration.In this study,we identified and characterized a new flo...N6-Methyladenosine(m^(6)A)is one of the most abundant modifications of eukaryotic mRNA,but its comprehensive biological functionality remains further exploration.In this study,we identified and characterized a new flowering-promoting gene,EARLY HEADING DATE6(EHD6),in rice.EHD6 encodes an RNA recognition motif(RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein(RNP)granules and can bind both m^(6)A-modified RNA and unmodified RNA indiscriminately.We found that EHD6 can physically interact with YTH07,a YTH(YT521-B homology)domain-containing m^(6)A reader.We showed that their interaction enhances the binding of an m^(6)A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation.Within these condensates,the mRNA of a rice flowering repressor,CONSTANS-like 4(OsCOL4),becomes sequestered,leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway.Taken together,these results not only shed new light on the molecular mechanism of efficient m^(6)A recognition by the collaboration between an RNA binding protein and YTH family m^(6)A reader,but also uncover the potential for m^(6)A-mediated translation regulation through phaseseparated ribonucleoprotein condensation in rice.展开更多
N^(6)-methyladenosine(m^(6)A)is the most abundant eukaryotic mRNA modification and is involved in various biological processes.Increasing evidence has implicated that m^(6)Amodification is an important anti-viral defe...N^(6)-methyladenosine(m^(6)A)is the most abundant eukaryotic mRNA modification and is involved in various biological processes.Increasing evidence has implicated that m^(6)Amodification is an important anti-viral defense mechanism in mammals and plants,but it is largely unknown how m^(6)Aregulates viral infection in plants.Here we report the dynamic changes and functional anatomy of m^(6)Ain Nicotiana benthamiana and Solanum lycopersicum during Pepino mosaic virus(PepMV)infection.m^(6)Amodification in the PepMV RNA genome is conserved in these two species.Overexpression of the m^(6)Awriters,mRNA adenosine methylase A(MTA),and HAKAI inhibit the PepMV RNA accumulation accompanied by increased viral m^(6)Amodifications,whereas deficiency of these writers decreases the viral RNA m^(6)Alevels but enhances virus infection.Further study reveals that the cytoplasmic YTH-domain family protein NbECT2A/2B/2C as m^(6)Areaders are involved in anti-viral immunity.Protein-protein interactions indicate that NbECT2A/2B/2C interact with nonsense-mediated mRNA decay(NMD)-related proteins,including NbUPF3 and NbSMG7,but not with NbUPF1.m^(6)Amodification-mediated restriction to PepMV infection is dependent on NMD-related factors.These findings provide new insights into the functionality of m^(6)Aanti-viral activity and reveal a distinct immune response that NMD factors recognize the m^(6)Areaders-viral m^(6)ARNA complex for viral RNA degradation to limit virus infection in plants.展开更多
Foxtail millet(Setaria italica),a vital drought-resistant crop,plays a significant role in ensuring food and nutritional security.However,its drought resistance mechanism is not fully understood.N6-methyladenosine(m^(...Foxtail millet(Setaria italica),a vital drought-resistant crop,plays a significant role in ensuring food and nutritional security.However,its drought resistance mechanism is not fully understood.N6-methyladenosine(m^(6)A)modification of RNA,a prevalent epi-transcriptomic modification in eukaryotes,provides a binding site for m^(6)A readers and affects plant growth and stress responses by regulating RNA metabolism.In this study,we unveiled that the YT521-B homology(YTH)family gene SiYTH1 positively regulated the drought tolerance of foxtail millet.Notably,the siyth1 mutant exhibited reduced stomatal closure and augmented accumulation of excessive H_(2)O_(2)under drought stress.Further investigations demonstrated that SiYTH1 positively regulated the transcripts harboring m^(6)A modification related to stomatal closure and reactive oxygen species(ROS)scavenging under drought stress.SiYTH1 was uniformly distributed in the cytoplasm of SiYTH1-GFP transgenic foxtail millet.It formed dynamic liquid-like SiYTH1 cytosol condensates in response to drought stress.Moreover,the cytoplasmic protein SiYTH1 was identified as a distinct m^(6)A reader,facilitating the stabilization of its directly bound SiARDP and ROS scavenging-related transcripts under drought stress.Furthermore,natural variation analysis revealed SiYTH1AGTG as the dominant allele responsible for drought tolerance in foxtail millet.Collectively,this study provides novel insights into the intricate mechanism of m^(6)A reader-mediated drought tolerance and presents a valuable genetic resource for improving drought tolerance in foxtail millet breeding.展开更多
N^(6)-methyladenosine(m^(6)A),which is added,removed,and interpreted by m^(6)A writers,erasers,and readers,respectively,is the most abundant modification in eukaryotic mRNAs.The m^(6)A marks play a pivotal role in the...N^(6)-methyladenosine(m^(6)A),which is added,removed,and interpreted by m^(6)A writers,erasers,and readers,respectively,is the most abundant modification in eukaryotic mRNAs.The m^(6)A marks play a pivotal role in the regulation of floral transition in plants.FLOWERING LOCUS K(FLK),an RNA-binding protein harboring K-homology(KH)motifs,is known to regulate floral transition by repressing the levels of a key floral repressor FLOWERING LOCUS C(FLC)in Arabidopsis.However,the molecular mechanism underlying FLK-mediated FLC regulation remains unclear.In this study,we identified FLK as a novel mRNA m^(6)A reader protein that directly binds the m^(6)A site in the 3ʹ-untranslated region of FLC transcripts to repressing FLC levels by reducing its stability and splicing.Importantly,FLK binding of FLC transcripts was abolished in vir-1,an m^(6)A writer mutant,and the late-flowering phenotype of the flk mutant could not be rescued by genetic complementation using the mutant FLKm gene,in which the m^(6)A reader encoding function was eliminated,indicating that FLK binds and regulates FLC expression in an m^(6)A-dependent manner.Collectively,our study has addressed a long-standing question of how FLK regulates FLC transcript levels and established a molecular link between the FLK-mediated recognition of m^(6)A modifications on FLC transcripts and floral transition in Arabidopsis.展开更多
N^6-methyladenosine(m^6A)emerges as an important modification in eukaryotic mRNAs.m^6A has first been reported in 1974,and its functional significance in mammalian gene regulation and importance for proper development...N^6-methyladenosine(m^6A)emerges as an important modification in eukaryotic mRNAs.m^6A has first been reported in 1974,and its functional significance in mammalian gene regulation and importance for proper development have been well established.An arsenal of writer,eraser,and reader proteins accomplish deposition,removal,and interpretation of the m^6A mark,resulting in dynamic function.This led to the concept of an epitranscriptome,the compendium of RNA species with chemical modification ofthe nucleobases in the cell,in analogy to the epigenome.While m^6A has long been known to also exist in plant mRNAs,proteins involved in m^6A metabolism have only recently been detected by mutant analysis,homology search,and mRNA interactome capture in the reference plant Arabidopsis thaliana.Dysregulation ofthe m^6A modification causes severe developmental abnormalities of leaves and roots and altered timing of reproductive development.Furthermore,m^6A modification affects viral infection.Here,we discuss recent progress in identifying m^6A sites transcriptome-wide,in identifying the molecular players involved in writing,removing,and reading the mark,and in assigning functions to this RNA modification in 4.thaliana.We highlight similarities and differences to m^6A modification in mammals and provide an outlook on important questions that remain to be addressed.展开更多
Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts ...Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the GP.Similar to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 mRNA.Igf2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their degradation.These findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.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
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
N6-methyladenine(m^(6)A)is the most abundant RNA modification in mammalian messenger RNAs(mRNAs),which participates in and regulates many important biological activities,such as tissue development and stem cell differ...N6-methyladenine(m^(6)A)is the most abundant RNA modification in mammalian messenger RNAs(mRNAs),which participates in and regulates many important biological activities,such as tissue development and stem cell differentiation.Due to an improved understanding of m^(6)A,researchers have discovered that the biological function of m^(6)A can be linked to many stages of mRNA metabolism and that m^(6)A can regulate a variety of complex biological processes.In addition to its location on mammalian mRNAs,m^(6)A has been identified on viral transcripts.m^(6)A also plays important roles in the life cycle of many viruses and in viral replication in host cells.In this review,we briefly introduce the detection methods of m^(6)A,the m^(6)A-related proteins,and the functions of m^(6)A.We also summarize the effects of m^(6)A-related proteins on viral replication and infection.We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses,and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication.We also anticipate that this review can stimulate collaborative research from different fields,such as chemistry,biology,and medicine,and promote the development of antiviral drugs and vaccines.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82030071 (to JH),82272495 (to YC)Science and Technology Major Project of Changsha,No.kh2103008 (to JH)Graduate Students’ Independent Innovative Projects of Hunan Province,No.CX20230311 (to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
基金supported by the National Natural Science Foundation of China(No.81770609,81970534,82100627)the University Synergy Innovation Program of Anhui Province,China(No.GXXT-2019-045)the Natural Science Foundation of Anhui Province,China(No.2108085QH311).
文摘N6-methyladenosine(m^(6)A)is a dynamic and reversible epigenetic regulation.As the most prevalent internal post-transcriptional modification in eukaryotic RNA,it participates in the regulation of gene expression through various mechanisms,such as mRNA splicing,nuclear export,localization,translation efficiency,mRNA stability,and structural transformation.The involvement of m^(6)A in the regulation of gene expression depends on the specific recognition of m^(6)A-modified RNA by reader proteins.In the pathogenesis and treatment of liver disease,studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m^(6)A modification,in which abnormal expression of reader proteins determines the fate of these gene transcripts.In this review,we introduce m^(6)A readers,summarize the recognition and regulatory mechanisms of m^(6)A readers on mRNA,and focus on the biological functions and mechanisms of m^(6)A readers in liver cancer,viral hepatitis,non-alcoholic fatty liver disease(NAFLD),hepatic fibrosis(HF),acute liver injury(ALI),and other liver diseases.This information is expected to be of high value to researchers deciphering the links between m^(6)A readers and human liver diseases.
基金supported by the Key Laboratory of Biology,Genetics and Breeding of Japonica Rice in Mid-lower Yangtze River,Ministry of Agriculture and Rural Affairs,China,and the Jiangsu Collaborative Innovation Center for Modern Crop Production,China.Funding for this work was provided by the National Key Research and Development Program of China(2020YFE0202300 and 2021YFD1200504)the National Natural Science Foundation of China(31971910 and 32272115)+1 种基金the National Science Foundation of Jiangsu Province(BK20212010 and BK20230038)the Foundation of Biological Breeding Zhongshan Lab(BM2022008-03,ZSBBL-KY2023-04,and ZSBBL-KY2023-06).
文摘N6-Methyladenosine(m^(6)A)is one of the most abundant modifications of eukaryotic mRNA,but its comprehensive biological functionality remains further exploration.In this study,we identified and characterized a new flowering-promoting gene,EARLY HEADING DATE6(EHD6),in rice.EHD6 encodes an RNA recognition motif(RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein(RNP)granules and can bind both m^(6)A-modified RNA and unmodified RNA indiscriminately.We found that EHD6 can physically interact with YTH07,a YTH(YT521-B homology)domain-containing m^(6)A reader.We showed that their interaction enhances the binding of an m^(6)A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation.Within these condensates,the mRNA of a rice flowering repressor,CONSTANS-like 4(OsCOL4),becomes sequestered,leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway.Taken together,these results not only shed new light on the molecular mechanism of efficient m^(6)A recognition by the collaboration between an RNA binding protein and YTH family m^(6)A reader,but also uncover the potential for m^(6)A-mediated translation regulation through phaseseparated ribonucleoprotein condensation in rice.
基金supported by the National Key Research and Development Program of China (2021YFD1400400) to Fangfang Lithe National Natural Science Foundation of China (32172385 and 31930089) to Fangfang Li and Xueping Zhou, respectively
文摘N^(6)-methyladenosine(m^(6)A)is the most abundant eukaryotic mRNA modification and is involved in various biological processes.Increasing evidence has implicated that m^(6)Amodification is an important anti-viral defense mechanism in mammals and plants,but it is largely unknown how m^(6)Aregulates viral infection in plants.Here we report the dynamic changes and functional anatomy of m^(6)Ain Nicotiana benthamiana and Solanum lycopersicum during Pepino mosaic virus(PepMV)infection.m^(6)Amodification in the PepMV RNA genome is conserved in these two species.Overexpression of the m^(6)Awriters,mRNA adenosine methylase A(MTA),and HAKAI inhibit the PepMV RNA accumulation accompanied by increased viral m^(6)Amodifications,whereas deficiency of these writers decreases the viral RNA m^(6)Alevels but enhances virus infection.Further study reveals that the cytoplasmic YTH-domain family protein NbECT2A/2B/2C as m^(6)Areaders are involved in anti-viral immunity.Protein-protein interactions indicate that NbECT2A/2B/2C interact with nonsense-mediated mRNA decay(NMD)-related proteins,including NbUPF3 and NbSMG7,but not with NbUPF1.m^(6)Amodification-mediated restriction to PepMV infection is dependent on NMD-related factors.These findings provide new insights into the functionality of m^(6)Aanti-viral activity and reveal a distinct immune response that NMD factors recognize the m^(6)Areaders-viral m^(6)ARNA complex for viral RNA degradation to limit virus infection in plants.
基金This work was supported by the National Key R&D Program of China(2023YFD1200700/2023YFD1200702/2018YFD1000700/2018YFD1000704).
文摘Foxtail millet(Setaria italica),a vital drought-resistant crop,plays a significant role in ensuring food and nutritional security.However,its drought resistance mechanism is not fully understood.N6-methyladenosine(m^(6)A)modification of RNA,a prevalent epi-transcriptomic modification in eukaryotes,provides a binding site for m^(6)A readers and affects plant growth and stress responses by regulating RNA metabolism.In this study,we unveiled that the YT521-B homology(YTH)family gene SiYTH1 positively regulated the drought tolerance of foxtail millet.Notably,the siyth1 mutant exhibited reduced stomatal closure and augmented accumulation of excessive H_(2)O_(2)under drought stress.Further investigations demonstrated that SiYTH1 positively regulated the transcripts harboring m^(6)A modification related to stomatal closure and reactive oxygen species(ROS)scavenging under drought stress.SiYTH1 was uniformly distributed in the cytoplasm of SiYTH1-GFP transgenic foxtail millet.It formed dynamic liquid-like SiYTH1 cytosol condensates in response to drought stress.Moreover,the cytoplasmic protein SiYTH1 was identified as a distinct m^(6)A reader,facilitating the stabilization of its directly bound SiARDP and ROS scavenging-related transcripts under drought stress.Furthermore,natural variation analysis revealed SiYTH1AGTG as the dominant allele responsible for drought tolerance in foxtail millet.Collectively,this study provides novel insights into the intricate mechanism of m^(6)A reader-mediated drought tolerance and presents a valuable genetic resource for improving drought tolerance in foxtail millet breeding.
基金supported by grants from 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,and the New Breeding Technologies Development Program(PJ01652401)Rural Development Administration,Republic of Korea(to H.K.).
文摘N^(6)-methyladenosine(m^(6)A),which is added,removed,and interpreted by m^(6)A writers,erasers,and readers,respectively,is the most abundant modification in eukaryotic mRNAs.The m^(6)A marks play a pivotal role in the regulation of floral transition in plants.FLOWERING LOCUS K(FLK),an RNA-binding protein harboring K-homology(KH)motifs,is known to regulate floral transition by repressing the levels of a key floral repressor FLOWERING LOCUS C(FLC)in Arabidopsis.However,the molecular mechanism underlying FLK-mediated FLC regulation remains unclear.In this study,we identified FLK as a novel mRNA m^(6)A reader protein that directly binds the m^(6)A site in the 3ʹ-untranslated region of FLC transcripts to repressing FLC levels by reducing its stability and splicing.Importantly,FLK binding of FLC transcripts was abolished in vir-1,an m^(6)A writer mutant,and the late-flowering phenotype of the flk mutant could not be rescued by genetic complementation using the mutant FLKm gene,in which the m^(6)A reader encoding function was eliminated,indicating that FLK binds and regulates FLC expression in an m^(6)A-dependent manner.Collectively,our study has addressed a long-standing question of how FLK regulates FLC transcript levels and established a molecular link between the FLK-mediated recognition of m^(6)A modifications on FLC transcripts and floral transition in Arabidopsis.
文摘N^6-methyladenosine(m^6A)emerges as an important modification in eukaryotic mRNAs.m^6A has first been reported in 1974,and its functional significance in mammalian gene regulation and importance for proper development have been well established.An arsenal of writer,eraser,and reader proteins accomplish deposition,removal,and interpretation of the m^6A mark,resulting in dynamic function.This led to the concept of an epitranscriptome,the compendium of RNA species with chemical modification ofthe nucleobases in the cell,in analogy to the epigenome.While m^6A has long been known to also exist in plant mRNAs,proteins involved in m^6A metabolism have only recently been detected by mutant analysis,homology search,and mRNA interactome capture in the reference plant Arabidopsis thaliana.Dysregulation ofthe m^6A modification causes severe developmental abnormalities of leaves and roots and altered timing of reproductive development.Furthermore,m^6A modification affects viral infection.Here,we discuss recent progress in identifying m^6A sites transcriptome-wide,in identifying the molecular players involved in writing,removing,and reading the mark,and in assigning functions to this RNA modification in 4.thaliana.We highlight similarities and differences to m^6A modification in mammals and provide an outlook on important questions that remain to be addressed.
基金supported by the National Key R&D Program of China(2018YFD0901201 and 2019YFA0802801)China Agricultural Research System(CARS-46)+3 种基金the National Natural Science Foundation of China(31870820)the Innovative Research Group Program of Hubei Province(2020CFA017)the Medical Science Advancement Program of Wuhan University(TFJC2018004)the Fundamental Research Funds for the Central Universities(2042019kf0207)。
文摘Bucky ball(Buc)is involved in germ plasm(GP)assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism.The present study demonstrates that an m^(6)A reader Igf2bp3 interacts and colocalizes with Buc in the GP.Similar to the loss of Buc,the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification,which can be partially restored by the injection of igf2 bp3 mRNA.Igf2bp3 binds to m^(6)A-modified GPorganizer and GP mRNAs in an m^(6)A-dependent manner and prevents their degradation.These findings indicate that the functions of Igf2bp3,a direct effector protein of Buc,in GP mRNA expression and GP assembly involve m^(6)A-dependent regulation;these results emphasize a critical role of m^(6)A modification in the process of GP assembly.
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 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the financial support provided by the National Natural Science Foundation of China(Grant No.21907077 to YW,Grant Nos.91753201 and 21721005 to XZ)the Postdoctoral Innovative Talent Support Program of China(Grant No.BX20180228 to YW)the China Postdoctoral Science Foundation(Grant No.2019M652691 to YW).
文摘N6-methyladenine(m^(6)A)is the most abundant RNA modification in mammalian messenger RNAs(mRNAs),which participates in and regulates many important biological activities,such as tissue development and stem cell differentiation.Due to an improved understanding of m^(6)A,researchers have discovered that the biological function of m^(6)A can be linked to many stages of mRNA metabolism and that m^(6)A can regulate a variety of complex biological processes.In addition to its location on mammalian mRNAs,m^(6)A has been identified on viral transcripts.m^(6)A also plays important roles in the life cycle of many viruses and in viral replication in host cells.In this review,we briefly introduce the detection methods of m^(6)A,the m^(6)A-related proteins,and the functions of m^(6)A.We also summarize the effects of m^(6)A-related proteins on viral replication and infection.We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses,and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication.We also anticipate that this review can stimulate collaborative research from different fields,such as chemistry,biology,and medicine,and promote the development of antiviral drugs and vaccines.