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 m5C oxidation in messenger RNA. Here, we describe a previously unc...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2021-01, Vol.296, p.100087-100087, Article 100087
Main Authors: Shen, Hui, Ontiveros, Robert Jordan, Owens, Michael C., Liu, Monica Yun, Ghanty, Uday, Kohli, Rahul M., Liu, Kathy Fange
Format: Article
Language:English
Subjects:
5-methylcytocine
5-Methylcytosine - chemistry
5-Methylcytosine - metabolism
Animals
demethylation
Dioxygenases
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Embryonic Stem Cells - metabolism
Mice
Mice, Knockout
Protein Biosynthesis
Proto-Oncogene Proteins - chemistry
Proto-Oncogene Proteins - metabolism
RNA modification
RNA, Transfer - chemistry
RNA, Transfer - metabolism
transfer RNA
translational regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 m5C oxidation in messenger RNA. Here, we describe a previously uncharacterized role of TET-mediated m5C oxidation in transfer RNA (tRNA). We found that the TET-mediated oxidation product 5-hydroxylmethylcytosine (hm5C) is specifically enriched in tRNA inside cells and that the oxidation activity of TET2 on m5C in tRNAs can be readily observed in vitro. We further observed that hm5C 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 hm5C and a decrease in m5C in tRNAs relative to uninduced cells. Strikingly, we also show that TET2-mediated m5C 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA120.014226