Details
| Original language | English |
|---|---|
| Pages (from-to) | 7451-7464 |
| Number of pages | 14 |
| Journal | Nucleic acids research |
| Volume | 51 |
| Issue number | 14 |
| Early online date | 19 Jun 2023 |
| Publication status | Published - 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 subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Genetics
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In: Nucleic acids research, Vol. 51, No. 14, 11.08.2023, p. 7451-7464.
Research output: Contribution to journal › Article › Research › peer review
}
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.
UR - http://www.scopus.com/inward/record.url?scp=85167844494&partnerID=8YFLogxK
U2 - 10.1093/nar/gkad529
DO - 10.1093/nar/gkad529
M3 - Article
C2 - 37334828
AN - SCOPUS:85167844494
VL - 51
SP - 7451
EP - 7464
JO - Nucleic acids research
JF - Nucleic acids research
SN - 0301-5610
IS - 14
ER -