ArticlePloS one2016
IDH1/2 Mutants Inhibit TET-Promoted Oxidation of RNA 5mC to 5hmC.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis.Cancer discovery · 2024Article
- Article
- Phenotypic and transcriptomic impact of expressing mammalian TET2 in theEpigenetics · 2023Article
- The Tet2-Upf1 complex modulates mRNA stability under stress conditions.Frontiers in genetics · 2023Article
- Tet Enzymes-Mediated DNA 5hmC Modification in Cerebral Ischemic and Hemorrhagic Injury.Neurotoxicity research · 2022Review
- Integrative analysis of CBR1 as a prognostic factor associated with IDH-mutant glioblastoma in the Chinese population.American journal of translational research · 2022Article
- Structure and Function of TET Enzymes.Advances in experimental medicine and biology · 2022Article
- The Potential Equivalents ofCancers · 2021Review
- Discovery of an Unnatural DNA Modification Derived from a Natural Secondary Metabolite.Cell chemical biology · 2021Article
- The role of RNA mInternational journal of biological sciences · 2021Review
- The epitranscriptome in stem cell biology and neural development.Neurobiology of disease · 2020Review
- Pan-cancer analysis reveals synergistic effects of CDK4/6i and PARPi combination treatment in RB-proficient and RB-deficient breast cancer cells.Cell death & disease · 2020Article
- Global DNA Methylation Patterns in Human Gliomas and Their Interplay with Other Epigenetic Modifications.International journal of molecular sciences · 2019Review
- Selectivity and Promiscuity in TET-Mediated Oxidation of 5-Methylcytosine in DNA and RNA.Biochemistry · 2019Article
- PML Recruits TET2 to Regulate DNA Modification and Cell Proliferation in Response to Chemotherapeutic Agent.Cancer research · 2018Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TETs (TET1/2/3) play critical roles in multi cellular processes through DNA demethylation driven by oxidation of DNA 5mdC to 5hmdC. Interestingly, recent studies indicated that TETs also oxidate RNA 5mC to 5hmC. However, little is known about the distribution of RNA 5hmC and the regulatory mechanism of RNA 5hmC in human. Here, we show that 5hmC is enriched in mRNA, and IDH1/2 mutants inhibit TET-promoted oxidation of RNA 5mC to 5hmC. Since IDH1/2 mutations have been described to block the DNA oxidative activity of TETs, we hypothesized that IDH1/2 mutations might also inhibit the RNA oxidative activity of TETs. To evaluate the role of IDH1/2 mutations in RNA 5hmC, TETs with/without IDH1/2 mutants were overexpressed in human HEK293 cells. Resultant DNA and RNA were digested and analyzed by triple-quadrupole LC mass spectrometer. DNA 5hmdC and RNA 5hmC modifications were quantified with external calibration curves of appropriate standards. It was found that compared with total RNA (5hmC/C: less than 2 X 10-7), mRNA showed much higher 5hmC level (5hmC/C: ∼7 X 10-6). Further study indicated that IDH1/2 mutants showed significant ability to inhibit TET-promoted RNA5hmC. Consistent with this result, overexpression of IDH1/2 mutants also inhibited TET catalytic domain-promoted oxidation of RNA. In this study, we show not only the enrichment of 5hmC in mRNA, but also a regulatory mechanism of RNA 5hmC-IDH1/2 mutations inhibit TET-promoted RNA 5hmC, which suggests an involvement of IDH1/2 mutations in tumorigenesis through the deregulation of RNA biology.
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