Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

Externe Organisationen

  • Nanjing Agricultural University
  • Nanjing Forest Police College
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Details

OriginalspracheEnglisch
Seiten (von - bis)7451-7464
Seitenumfang14
FachzeitschriftNucleic acids research
Jahrgang51
Ausgabenummer14
Frühes Online-Datum19 Juni 2023
PublikationsstatusVeröffentlicht - 11 Aug. 2023

Abstract

5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2'-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.

ASJC Scopus Sachgebiete

  • Biochemie, Genetik und Molekularbiologie (insg.)
  • Genetik

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Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA. / Gao, Shangyu; Sun, Yu; Chen, Xiaoguang et al.
in: Nucleic acids research, Jahrgang 51, Nr. 14, 11.08.2023, S. 7451-7464.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Gao S, Sun Y, Chen X, Zhu C, Liu X, Wang W et al. Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA. Nucleic acids research. 2023 Aug 11;51(14):7451-7464. Epub 2023 Jun 19. doi: 10.1093/nar/gkad529
Gao, Shangyu ; Sun, Yu ; Chen, Xiaoguang et al. / Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA. in: Nucleic acids research. 2023 ; Jahrgang 51, Nr. 14. S. 7451-7464.
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title = "Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA",
abstract = "5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2'-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.",
author = "Shangyu Gao and Yu Sun and Xiaoguang Chen and Changhua Zhu and Xiaoye Liu and Wenlei Wang and Lijun Gan and Yanwu Lu and Frank Schaarschmidt and Marco Herde and Witte, {Claus Peter} and Mingjia Chen",
note = "Funding Information: The Fundamental Research Funds for the Central Universities [YDZX2023013]; the Deutsche Forschungsgemeinschaft (DFG) [CH2292/1-1 to M.C. and C.-P.W., WI3411/8-1 and INST 187/741-1 FUGG to C.-P. W., and HE-5949/4-1 to M.H.]; the International Centre for Genetic Engineering and Biotechnology [CRP/CHN20-04_EC]; the National Natural Science Foundation of China [31900907]; the Natural Science Foundation of Jiangsu Province, China [BK20190528]; and Nanjing Agricultural University [start-up fund for advanced talents to M.C.]. Funding for open access charge: Nanjing Agricultural University, China.",
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Download

TY - JOUR

T1 - Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA

AU - Gao, Shangyu

AU - Sun, Yu

AU - Chen, Xiaoguang

AU - Zhu, Changhua

AU - Liu, Xiaoye

AU - Wang, Wenlei

AU - Gan, Lijun

AU - Lu, Yanwu

AU - Schaarschmidt, Frank

AU - Herde, Marco

AU - Witte, Claus Peter

AU - Chen, Mingjia

N1 - Funding Information: The Fundamental Research Funds for the Central Universities [YDZX2023013]; the Deutsche Forschungsgemeinschaft (DFG) [CH2292/1-1 to M.C. and C.-P.W., WI3411/8-1 and INST 187/741-1 FUGG to C.-P. W., and HE-5949/4-1 to M.H.]; the International Centre for Genetic Engineering and Biotechnology [CRP/CHN20-04_EC]; the National Natural Science Foundation of China [31900907]; the Natural Science Foundation of Jiangsu Province, China [BK20190528]; and Nanjing Agricultural University [start-up fund for advanced talents to M.C.]. Funding for open access charge: Nanjing Agricultural University, China.

PY - 2023/8/11

Y1 - 2023/8/11

N2 - 5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2'-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.

AB - 5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2'-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.

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U2 - 10.1093/nar/gkad529

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