The mRNA modification N^(6)-methyladenosine(m^(6)A)plays vital roles in plant development and biotic and abiotic stress responses.The RNA m^(6)A demethylase ALKBH9 B can remove m^(6)A in alfalfa mosaic virus RNA and p...The mRNA modification N^(6)-methyladenosine(m^(6)A)plays vital roles in plant development and biotic and abiotic stress responses.The RNA m^(6)A demethylase ALKBH9 B can remove m^(6)A in alfalfa mosaic virus RNA and plays roles in alfalfa mosaic virus infection in Arabidopsis.However,it is unknown whether ALKBH9 B also exhibits demethylation activity and has a biological role in endogenous plant mRNA.We demonstrated here that mRNA m^(6)A modification is induced by the phytohormone abscisic acid(ABA)and that ALKBH9 B has m^(6)A demethylation activity on endogenous mRNA.Knocking out ALKBH9 B led to hypersensitivity to ABA treatment during seed germination and early seedling development.We further showed that ALKBH9 B removes the m^(6)A modification in the ABA INSENSITIVE 1(ABI1)and BRI1-EMS-SUPPRESSOR 1(BES1)transcripts following ABA treatment,affecting the stability of these mRNAs.Furthermore,we determined that ALKBH9 B acts genetically upstream of the transcription factors ABI3 and ABI5,and its regulatory function in ABA responses depended on ABI3 and ABI5.Our findings reveal the important roles of the m^(6)A modification in ABA responses and highlight the role of ALKBH9 Bmediated m^(6)A demethylation in regulating ABA responses post-transcriptionally.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the Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciencessupported by the National Natural Science Foundation of China(nos.22225704,21820102008,92053109)+1 种基金the National Basic Research Program of China(2019YFA0802201)the Beijing Natural Science Foundation(Z200010)。
文摘The mRNA modification N^(6)-methyladenosine(m^(6)A)plays vital roles in plant development and biotic and abiotic stress responses.The RNA m^(6)A demethylase ALKBH9 B can remove m^(6)A in alfalfa mosaic virus RNA and plays roles in alfalfa mosaic virus infection in Arabidopsis.However,it is unknown whether ALKBH9 B also exhibits demethylation activity and has a biological role in endogenous plant mRNA.We demonstrated here that mRNA m^(6)A modification is induced by the phytohormone abscisic acid(ABA)and that ALKBH9 B has m^(6)A demethylation activity on endogenous mRNA.Knocking out ALKBH9 B led to hypersensitivity to ABA treatment during seed germination and early seedling development.We further showed that ALKBH9 B removes the m^(6)A modification in the ABA INSENSITIVE 1(ABI1)and BRI1-EMS-SUPPRESSOR 1(BES1)transcripts following ABA treatment,affecting the stability of these mRNAs.Furthermore,we determined that ALKBH9 B acts genetically upstream of the transcription factors ABI3 and ABI5,and its regulatory function in ABA responses depended on ABI3 and ABI5.Our findings reveal the important roles of the m^(6)A modification in ABA responses and highlight the role of ALKBH9 Bmediated m^(6)A demethylation in regulating ABA responses post-transcriptionally.
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.
