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

doi:10.1074/jbc.ra120.014226

Cited by 53 publications

(33 citation statements)

References 48 publications

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“…Similar to N6-methyladenosine (m6A), the m5C modification is dynamic and reversible. It is catalyzed by the NSUN family (NSUN1-7) [ 3 , 4 , 5 , 6 ] and DNMT2 [ 7 ], demethylated by the TET family [ 8 ] and ALKBH1 [ 9 ], and recognized by reader proteins ALYREF [ 10 ] and YBX1 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

Wang

Huang

Jiang

et al. 2022

IJMS

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The 5-methylcytosine (m5C) modification on an mRNA molecule is deposited by Nsun2 and its paralog Nsun6. While the physiological functions of Nsun2 have been carefully studied using gene knockout (KO) mice, the physiological functions of Nsun6 remain elusive. In this study, we generated an Nsun6-KO mouse strain, which exhibited no apparent phenotype in both the development and adult stages as compared to wild-type mice. Taking advantage of this mouse strain, we identified 80 high-confident Nsun6-dependent m5C sites by mRNA bisulfite sequencing in five different tissues and systematically analyzed the transcriptomic phenotypes of Nsun6-KO tissues by mRNA sequencing. Our data indicated that Nsun6 is not required for the homeostasis of these organs under laboratory housing conditions, but its loss may affect immune response in the spleen and oxidoreductive reaction in the liver under certain conditions. Additionally, we further investigated T-cell-dependent B cell activation in KO mice and found that Nsun6 is not essential for the germinal center B cell formation but is associated with the formation of antibody-secreting plasma cells. Finally, we found that Nsun6-mediated m5C modification does not have any evident influence on the stability of Nsun6 target mRNAs, suggesting that Nsun6-KO-induced phenotypes may be associated with other functions of the m5C modification or Nsun6 protein.

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Section: Introductionmentioning

confidence: 99%

A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

Wang

Huang

Jiang

et al. 2022

IJMS

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“…TET2 mediated oxidation of m5C in tRNA promotes translation in vitro. This suggests that TET2 may affect translation by affecting tRNA methylation, and reveals the roles of TET enzyme in regulating gene expression (Shen et al, 2021a) (Figure 1B).…”

Section: M5c Modificationmentioning

confidence: 87%

RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

et al. 2021

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the world. Despite considerable progress in the diagnosis, treatment and prognosis of CVDs, new diagnostic biomarkers and new therapeutic measures are urgently needed to reduce the mortality of CVDs and improve the therapeutic effect. RNA methylations regulate almost all aspects of RNA processing, such as RNA nuclear export, translation, splicing and non-coding RNA processing. In view of the importance of RNA methylations in the pathogenesis of diseases, this work reviews the molecular structures, biological functions of five kinds of RNA methylations (m6A, m5C, m1a, m6am and m7G) and their effects on CVDs, including pulmonary hypertension, hypertension, vascular calcification, cardiac hypertrophy, heart failure. In CVDs, m6A “writers” catalyze the installation of m6A on RNAs, while “erasers” remove these modifications. Finally, the “readers” of m6A further influence the mRNA splicing, nuclear export, translation and degradation. M5C, m1A, m6Am and m7G are new types of RNA methylations, their roles in CVDs need to be further explored. RNA methylations have become a new research hotspot and the roles in CVDs is gradually emerging, the review of the molecular characteristics, biological functions and effects of RNA methylation on CVDs will contribute to the elucidation of the pathological mechanisms of CVDs and the discovery of new diagnostic markers and therapeutic targets of CVDs.

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“…5mrC has recently gained attention as a key posttranscriptional modification of RNA. Increasingly, evidence suggests that 5mrC modification is involved in a variety of cellular functions such as mRNA stability, gene transcription and tRNA translation [46][47][48]. In addition, 5mrC modification in RNA is linked with human diseases such as tumorigenesis [46].…”

Section: Significance Of Functional Flexibility On Rnamentioning

confidence: 99%

Bifunctional Role of Fe(II)/2OG-Dependent TET Family 5-Methylcytosine Dioxygenases and ALKBH2,3 in Modified Cytosine Demethylation

Dey

2022

BioChem

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Three forms of methylated cytosines are present in the eukaryotic genome: 3-methylcytosine, 4-methylcytosine and 5-methylcytosine. 3-methylcytosines create methyl lesions, which impair local DNA function and flexibility, resulting in replication and transcription error. On the other hand, 5-methylcytosine is usually present at the gene promoter which blocks transcription and translation. Fe(II)/2OG-dependent nucleic acid-modifying enzymes are the class of enzymes responsible for the demethylation of these modified cytosines. ALKBH2 and 3 remove 3-methylcytosine via a one-step direct demethylation process. On the other hand, active demethylation of 5mC is initiated by Ten-Eleven Translocation (TET)-family dioxygenases. Via oxidative demethylation, TET1-3 converts 5mC into 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Remarkably, recent findings demonstrate that ALKBH2,3 possess oxidative demethylation properties, along with direct demethylation. On the other hand, the TET family of enzymes possess direct demethylation properties along with oxidative demethylation. Here we review the importance of methylated cytosines in human DNA, their origin, function and removal. In addition, we discuss the recent findings of extraordinary flexibility of Fe(II)/2OG-dependent nucleic acid-modifying enzymes ALKBH2,3 and TET family of enzymes in cytosine demethylation, as well as their impact on epigenetics.

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TET-mediated 5-methylcytosine oxidation in tRNA promotes translation

Cited by 53 publications

References 48 publications

A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

Bifunctional Role of Fe(II)/2OG-Dependent TET Family 5-Methylcytosine Dioxygenases and ALKBH2,3 in Modified Cytosine Demethylation

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