SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

Du, Yuzhang; Hou, Guofang; Zhang, Hailong; Dou, Jinzhuo; He, Jianfeng; Guo, Yanming; Li, Lian; Chen, Ran; Wang, Yanli; Deng, Rong; Huang, Jian; Jiang, Bin; Xu, Ming; Cheng, Jinke; Chen, Guoqiang; Zhao, Xian; Yu, Jianxiu

doi:10.1093/nar/gky156

Cited by 242 publications

(187 citation statements)

References 48 publications

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“…N6-methyladenosine (m6A) of RNA has been proposed as a new layer of epigenetic regulation. This biochemical process is proved to play important roles in regulation of cell growth, differentiation, and self-renewal through controlling RNA splicing, translation and stability [23,26,27]. Previous studies identified m6A as a predominant modification of mRNAs [7,23].…”

Section: Discussionmentioning

confidence: 99%

METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST

et al. 2020

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Background: N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulation in eukaryotic cells. However, understanding of m6A in colorectal cancer (CRC) is very limited. We designed this study to investigate the role of m6A in CRC.Methods: Expression level of METTL14 was extracted from public database and tissue array to investigate the clinical relevance of METTL14 in CRC. Next, gain/loss of function experiment was used to define the role of METTL14 in the progression of CRC. Moreover, transcriptomic sequencing (RNA-seq) was applied to screen the potential targets of METTL14. The specific binding between METTL14 and presumed target was verified by RNA pull-down and RNA immunoprecipitation (RIP) assay. Furthermore, rescue experiment and methylated RNA immunoprecipitation (Me-RIP) were performed to uncover the mechanism.Results: Clinically, loss of METTL14 correlated with unfavorable prognosis of CRC patients. Functionally, knockdown of METTL14 drastically enhanced proliferative and invasive ability of CRC cells in vitro and promoted tumorigenicity and metastasis in vivo. Mechanically, RNA-seq and Me-RIP identified lncRNA XIST as the downstream target of METTL14. Knockdown of METTL14 substantially abolished m6A level of XIST and augmented XIST expression. Moreover, we found that m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. Consistently, XIST expression negatively correlated with METTL14 and YTHDF2 in CRC tissues.Conclusion: Our findings highlight the function and prognostic value of METTL14 in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology.

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Section: Discussionmentioning

confidence: 99%

METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST

et al. 2020

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“…More recently, SUMOylation of METTL3 has also been shown to regulate its methyltransferase activity (Du et al . ).…”

Section: Closing Remarks and Outlookmentioning

confidence: 97%

“…One line of evidence shows that posttranslational modification of FTO by ubiquitination regulates its proteasomal degradation, nuclear translocation, and demethylase activity (Tai et al 2017;Zhu et al 2018). More recently, SUMOylation of METTL3 has also been shown to regulate its methyltransferase activity (Du et al 2018).…”

Section: Closing Remarks and Outlookmentioning

confidence: 99%

The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

Widagdo

Anggono

2018

Journal of Neurochemistry

127

103

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Research over the past decade has provided strong support for the importance of various epigenetic mechanisms, including DNA and histone modifications in regulating activity-dependent gene expression in the mammalian central nervous system. More recently, the emerging field of epitranscriptomics revealed an equally important role of post-transcriptional RNA modifications in shaping the transcriptomic landscape of the brain. This review will focus on the methylation of the adenosine base at the N6 position, termed N methyladenosine (m6A), which is the most abundant internal modification that decorates eukaryotic messenger RNAs. Given its prevalence and dynamic regulation in the adult brain, the m6A-epitranscriptome provides an additional layer of regulation on RNA that can be controlled in a context- and stimulus-dependent manner. Conceptually, m6A serves as a molecular switch that regulates various aspects of RNA function, including splicing, stability, localization, or translational control. The versatility of m6A function is typically determined through interaction or disengagement with specific classes of m6A-interacting proteins. Here we review recent advances in the field and provide insights into the roles of m6A in regulating brain function, from development to synaptic plasticity, learning, and memory. We also discuss how aberrant m6A signaling may contribute to neurodevelopmental and neuropsychiatric disorders.

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“…It's interesting that the size of METTL3 is about 100 kD in all of the samples and is larger than predicted. This result indicated that METTL3 in silkworm may be modified by SUMOylation (Du et al, ).…”

Section: Resultsmentioning

confidence: 95%

The role of N6‐methyladenosine modification on diapause in silkworm (Bombyx mori) strains that exhibit different voltinism

Jiang

Qian

et al. 2019

Molecular Reproduction Devel

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N6‐methyladenosine (m6A) plays a key role in regulating gene expression in myriad organisms. Diapause is an important plastic phenotype that allows insects to survive under specific environmental conditions. However, the diapause molecular mechanism remains unknown. In this study, we analyzed the phylogenetics of genes related to the m6A modification complex in the silkworm (Bombyx mori) based on identified sequences from other organisms. We detected the expression of these genes during different developmental phases from four strains with different voltinism. We also determined total m6A content in cells treated with different diapause hormone concentrations or eggs exposed to hydrochloric acid. Our data revealed that m6A‐modification‐related gene expression and m6A content were greater in diapause‐destinated compared to nondiapause‐destined strains. Our findings suggest that m6A modification may provide significant epigenetic regulation of diapause‐related genes in the silkworm.

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SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

Cited by 242 publications

References 48 publications

METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST

METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST

The m6A‐epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity

The role of N6‐methyladenosine modification on diapause in silkworm (Bombyx mori) strains that exhibit different voltinism

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