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TET-mediated 5-methylcytosine oxidation in tRNA promotes translation

Oxidation of 5-methylcytosine (5mC) in DNA by the ten-eleven translocation (TET) family of enzymes is indispensable for gene regulation in mammals. More recently, evidence has emerged to support a biological function for TET-mediated m(5)C oxidation in messenger RNA. Here, we describe a previously u...

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Autores principales: Shen, Hui, Ontiveros, Robert Jordan, Owens, Michael C., Liu, Monica Yun, Ghanty, Uday, Kohli, Rahul M., Liu, Kathy Fange
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949041/
https://www.ncbi.nlm.nih.gov/pubmed/33199375
http://dx.doi.org/10.1074/jbc.RA120.014226
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author Shen, Hui
Ontiveros, Robert Jordan
Owens, Michael C.
Liu, Monica Yun
Ghanty, Uday
Kohli, Rahul M.
Liu, Kathy Fange
author_facet Shen, Hui
Ontiveros, Robert Jordan
Owens, Michael C.
Liu, Monica Yun
Ghanty, Uday
Kohli, Rahul M.
Liu, Kathy Fange
author_sort Shen, Hui
collection PubMed
description Oxidation of 5-methylcytosine (5mC) in DNA by the ten-eleven translocation (TET) family of enzymes is indispensable for gene regulation in mammals. More recently, evidence has emerged to support a biological function for TET-mediated m(5)C oxidation in messenger RNA. Here, we describe a previously uncharacterized role of TET-mediated m(5)C oxidation in transfer RNA (tRNA). We found that the TET-mediated oxidation product 5-hydroxylmethylcytosine (hm(5)C) is specifically enriched in tRNA inside cells and that the oxidation activity of TET2 on m(5)C in tRNAs can be readily observed in vitro. We further observed that hm(5)C levels in tRNA were significantly decreased in Tet2 KO mouse embryonic stem cells (mESCs) in comparison with wild-type mESCs. Reciprocally, induced expression of the catalytic domain of TET2 led to an obvious increase in hm(5)C and a decrease in m(5)C in tRNAs relative to uninduced cells. Strikingly, we also show that TET2-mediated m(5)C oxidation in tRNA promotes translation in vitro. These results suggest TET2 may influence translation through impacting tRNA methylation and reveal an unexpected role for TET enzymes in regulating multiple nodes of the central dogma.
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spelling pubmed-79490412021-03-19 TET-mediated 5-methylcytosine oxidation in tRNA promotes translation Shen, Hui Ontiveros, Robert Jordan Owens, Michael C. Liu, Monica Yun Ghanty, Uday Kohli, Rahul M. Liu, Kathy Fange J Biol Chem Research Article Oxidation of 5-methylcytosine (5mC) in DNA by the ten-eleven translocation (TET) family of enzymes is indispensable for gene regulation in mammals. More recently, evidence has emerged to support a biological function for TET-mediated m(5)C oxidation in messenger RNA. Here, we describe a previously uncharacterized role of TET-mediated m(5)C oxidation in transfer RNA (tRNA). We found that the TET-mediated oxidation product 5-hydroxylmethylcytosine (hm(5)C) is specifically enriched in tRNA inside cells and that the oxidation activity of TET2 on m(5)C in tRNAs can be readily observed in vitro. We further observed that hm(5)C levels in tRNA were significantly decreased in Tet2 KO mouse embryonic stem cells (mESCs) in comparison with wild-type mESCs. Reciprocally, induced expression of the catalytic domain of TET2 led to an obvious increase in hm(5)C and a decrease in m(5)C in tRNAs relative to uninduced cells. Strikingly, we also show that TET2-mediated m(5)C oxidation in tRNA promotes translation in vitro. These results suggest TET2 may influence translation through impacting tRNA methylation and reveal an unexpected role for TET enzymes in regulating multiple nodes of the central dogma. American Society for Biochemistry and Molecular Biology 2020-11-23 /pmc/articles/PMC7949041/ /pubmed/33199375 http://dx.doi.org/10.1074/jbc.RA120.014226 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Shen, Hui
Ontiveros, Robert Jordan
Owens, Michael C.
Liu, Monica Yun
Ghanty, Uday
Kohli, Rahul M.
Liu, Kathy Fange
TET-mediated 5-methylcytosine oxidation in tRNA promotes translation
title TET-mediated 5-methylcytosine oxidation in tRNA promotes translation
title_full TET-mediated 5-methylcytosine oxidation in tRNA promotes translation
title_fullStr TET-mediated 5-methylcytosine oxidation in tRNA promotes translation
title_full_unstemmed TET-mediated 5-methylcytosine oxidation in tRNA promotes translation
title_short TET-mediated 5-methylcytosine oxidation in tRNA promotes translation
title_sort tet-mediated 5-methylcytosine oxidation in trna promotes translation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949041/
https://www.ncbi.nlm.nih.gov/pubmed/33199375
http://dx.doi.org/10.1074/jbc.RA120.014226
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