The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Kai Chen - One of the best experts on this subject based on the ideXlab platform.
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Publisher Correction: N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.
Nature chemical biology, 2019Co-Authors: Xiaoyun Wang, Kai Chen, Hao Chen, Jiabin Cai, Qing Dai, S. Kundhavai Natchiar, Yujiang Geno ShiAbstract:In the version of this article originally published, the references were incorrectly re-ordered during production. The hyphen in “N6-Methyladenosine” in the title was also superscript. The errors have been corrected in the HTML and PDF versions of the paper.
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n6 methyladenosine methyltransferase zcchc4 mediates ribosomal rna methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kundhavai S Natchiar, Ruitu Lv, Bruno P Klaholz, Zhike Lu, Kai Chen, Hao Chen, Chuan HeAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology. ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-Methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in cancer cells.
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N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kai Chen, Hao Chen, Jiabin Cai, Qing Dai, S. Kundhavai Natchiar, Yujiang Geno Shi, Fei Lan, Jia Fan, Bruno P KlaholzAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology.
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Development of Cell-Active N6-Methyladenosine RNA Demethylase FTO Inhibitor
Journal of the American Chemical Society, 2012Co-Authors: Baoen Chen, Kai Chen, Guifang Jia, Xiaotian Huang, Xueju Zhang, Shuying Peng, Meining Wang, Shouze GongAbstract:The direct nucleic acid repair dioxygenase FTO is an enzyme that demethylates N6-Methyladenosine (m6A) residues in mRNA in vitro and inside cells. FTO is the first RNA demethylase discovered that also serves a major regulatory function in mammals. Together with structure-based virtual screening and biochemical analyses, we report the first identification of several small-molecule inhibitors of human FTO demethylase. The most potent compound, the natural product rhein, which is neither a structural mimic of 2-oxoglutarate nor a chelator of metal ion, competitively binds to the FTO active site in vitro. Rhein also exhibits good inhibitory activity on m6A demethylation inside cells. These studies shed light on the development of powerful probes and new therapies for use in RNA biology and drug discovery.
Xiaoyun Wang - One of the best experts on this subject based on the ideXlab platform.
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Publisher Correction: N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.
Nature chemical biology, 2019Co-Authors: Xiaoyun Wang, Kai Chen, Hao Chen, Jiabin Cai, Qing Dai, S. Kundhavai Natchiar, Yujiang Geno ShiAbstract:In the version of this article originally published, the references were incorrectly re-ordered during production. The hyphen in “N6-Methyladenosine” in the title was also superscript. The errors have been corrected in the HTML and PDF versions of the paper.
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n6 methyladenosine methyltransferase zcchc4 mediates ribosomal rna methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kundhavai S Natchiar, Ruitu Lv, Bruno P Klaholz, Zhike Lu, Kai Chen, Hao Chen, Chuan HeAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology. ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-Methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in cancer cells.
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N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kai Chen, Hao Chen, Jiabin Cai, Qing Dai, S. Kundhavai Natchiar, Yujiang Geno Shi, Fei Lan, Jia Fan, Bruno P KlaholzAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology.
Yinsheng Wang - One of the best experts on this subject based on the ideXlab platform.
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position dependent effects of regioisomeric methylated adenine and guanine ribonucleosides on translation
Nucleic Acids Research, 2017Co-Authors: Xiaoxia Dai, Changjun You, Yinsheng WangAbstract:Reversible methylation of the N6 or N1 position of adenine in RNA has recently been shown to play significant roles in regulating the functions of RNA. RNA can also be alkylated upon exposure to endogenous and exogenous alkylating agents. Here we examined how regio-specific methylation at the hydrogen bonding edge of adenine and guanine in mRNA affects translation. When situated at the third codon position, the methylated nucleosides did not compromise the speed or accuracy of translation under most circumstances. When located at the first or second codon position, N1-methyladenosine (m1A) and m1G constituted robust blocks to both Escherichia coli and wheat germ extract translation systems, whereas N2-methylguanosine (m2G) moderately impeded translation. While m1A, m2G and N6-Methyladenosine (m6A) did not perturb translational fidelity, O6-methylguanosine (m6G) at the first and second codon positions was strongly and moderately miscoding, respectively, and it was decoded as an adenosine in both systems. The effects of methylated ribonucleosides on translation could be attributed to the methylation-elicited alterations in base pairing properties of the nucleobases, and the mechanisms of ribosomal decoding contributed to the position-dependent effects. Together, our study afforded important new knowledge about the modulation of translation by methylation of purine nucleobases in mRNA.
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simultaneous quantification of methylated cytidine and adenosine in cellular and tissue rna by nano flow liquid chromatography tandem mass spectrometry coupled with the stable isotope dilution method
Analytical Chemistry, 2015Co-Authors: Nicholas J Amato, Pengcheng Wang, Sara J Mcgowan, Laura J Niedernhofer, Yinsheng WangAbstract:The rising interest in understanding the functions, regulation, and maintenance of the epitranscriptome calls for robust and accurate analytical methods for the identification and quantification of post-transcriptionally modified nucleosides in RNA. Monomethylations of cytidine and adenosine are common post-transcriptional modifications in RNA. Herein, we developed an LC–MS/MS/MS coupled with the stable isotope-dilution method for the sensitive and accurate quantifications of 5-methylcytidine (m5C), 2′-O-methylcytidine (Cm), N6-Methyladenosine (m6A), and 2′-O-methyladenosine (Am) in RNA isolated from mammalian cells and tissues. Our results showed that the distributions of m5C, Cm and Am are tissue-specific. In addition, the 2′-O-methylated ribonucleosides (Cm and Am) are present at higher levels than the corresponding methylated nucleobase products (m5C and m6A) in total RNA isolated from mouse brain, pancreas, and spleen but not mouse heart. We also found that the levels of m5C, Cm, and Am are significa...
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Simultaneous Quantification of Methylated Cytidine and Adenosine in Cellular and Tissue RNA by Nano-Flow Liquid Chromatography–Tandem Mass Spectrometry Coupled with the Stable Isotope-Dilution Method
Analytical chemistry, 2015Co-Authors: Nicholas J Amato, Pengcheng Wang, Sara J Mcgowan, Laura J Niedernhofer, Yinsheng WangAbstract:The rising interest in understanding the functions, regulation, and maintenance of the epitranscriptome calls for robust and accurate analytical methods for the identification and quantification of post-transcriptionally modified nucleosides in RNA. Monomethylations of cytidine and adenosine are common post-transcriptional modifications in RNA. Herein, we developed an LC–MS/MS/MS coupled with the stable isotope-dilution method for the sensitive and accurate quantifications of 5-methylcytidine (m5C), 2′-O-methylcytidine (Cm), N6-Methyladenosine (m6A), and 2′-O-methyladenosine (Am) in RNA isolated from mammalian cells and tissues. Our results showed that the distributions of m5C, Cm and Am are tissue-specific. In addition, the 2′-O-methylated ribonucleosides (Cm and Am) are present at higher levels than the corresponding methylated nucleobase products (m5C and m6A) in total RNA isolated from mouse brain, pancreas, and spleen but not mouse heart. We also found that the levels of m5C, Cm, and Am are significa...
Zhike Lu - One of the best experts on this subject based on the ideXlab platform.
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n6 methyladenosine rna modification mediated cellular metabolism rewiring inhibits viral replication
Science, 2019Co-Authors: Zhike Lu, Panpan Li, Jiang Yang, Henan XuAbstract:Host cell metabolism can be modulated by viral infection, affecting viral survival or clearance. Yet the cellular metabolism rewiring mediated by the N6-Methyladenosine (m6A) modification in interactions between virus and host remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of the RNA m6A demethylase ALKBH5. This behavior increases the m6A methylation on α-ketoglutarate dehydrogenase (OGDH) messenger RNA (mRNA) to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of the metabolite itaconate that is required for viral replication. With reduced OGDH and itaconate production in vivo, Alkbh5-deficient mice display innate immune response–independent resistance to viral exposure. Our findings reveal that m6A RNA modification–mediated down-regulation of the OGDH-itaconate pathway reprograms cellular metabolism to inhibit viral replication, proposing potential targets for controlling viral infection.
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N6-Methyladenosine RNA modification–mediated cellular metabolism rewiring inhibits viral replication
Science, 2019Co-Authors: Zhike Lu, Panpan Li, Jiang Yang, Henan XuAbstract:Host cell metabolism can be modulated by viral infection, affecting viral survival or clearance. Yet the cellular metabolism rewiring mediated by the N6-Methyladenosine (m6A) modification in interactions between virus and host remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of the RNA m6A demethylase ALKBH5. This behavior increases the m6A methylation on α-ketoglutarate dehydrogenase (OGDH) messenger RNA (mRNA) to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of the metabolite itaconate that is required for viral replication. With reduced OGDH and itaconate production in vivo, Alkbh5-deficient mice display innate immune response–independent resistance to viral exposure. Our findings reveal that m6A RNA modification–mediated down-regulation of the OGDH-itaconate pathway reprograms cellular metabolism to inhibit viral replication, proposing potential targets for controlling viral infection.
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n6 methyladenosine methyltransferase zcchc4 mediates ribosomal rna methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kundhavai S Natchiar, Ruitu Lv, Bruno P Klaholz, Zhike Lu, Kai Chen, Hao Chen, Chuan HeAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology. ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-Methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in cancer cells.
Bruno P Klaholz - One of the best experts on this subject based on the ideXlab platform.
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n6 methyladenosine methyltransferase zcchc4 mediates ribosomal rna methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kundhavai S Natchiar, Ruitu Lv, Bruno P Klaholz, Zhike Lu, Kai Chen, Hao Chen, Chuan HeAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology. ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-Methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in cancer cells.
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N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation
Nature Chemical Biology, 2019Co-Authors: Xiaoyun Wang, Kai Chen, Hao Chen, Jiabin Cai, Qing Dai, S. Kundhavai Natchiar, Yujiang Geno Shi, Fei Lan, Jia Fan, Bruno P KlaholzAbstract:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology.
