MicroRNA-145 Modulates N6-Methyladenosine Levels by Targeting the 3′-Untranslated mRNA Region of the N6-Methyladenosine Binding YTH Domain Family 2 Protein

Yang, Zhe; Li, Jiong; Feng, Guoxing; Gao, Shan; Wang, Yuan; Zhang, Shuqin; Liu, Yunxia; Ye, Lihong; Li, Yueguo; Zhang, Xiaodong

doi:10.1074/jbc.m116.749689

Cited by 231 publications

(219 citation statements)

References 49 publications

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“…YTHDF2 was found to be up‐regulated in HCC, and miR‐145 was identified as an upstream regulatory factor to elevate m 6 A level by targeting YTHDF2 which was consistent with silencing of YTHDF2 78. In addition, YTHDF2 was also found to be significantly up‐regulated in prostate cancer tissues 79.…”

Section: The Dual Role Of M6a Modification In Human Cancerssupporting

confidence: 53%

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Wang

et al. 2018

J Cellular Molecular Medi

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As the most abundant and reversible RNA modification in eukaryotic cells, m6A triggers a new layer of epi‐transcription. M6A modification occurs through a methylation process modified by “writers” complexes, reversed by “erasers”, and exerts its role depending on various “readers”. Emerging evidence shows that there is a strong association between m6A and human diseases, especially cancers. Herein, we review bi‐aspects of m6A in regulating cancers mediated by the m6A‐associated proteins, which exert vital and specific roles in the development of various cancers. Generally, the m6A modification performs promotion or inhibition functions (dual role) in tumorigenesis and progression of various cancers, which suggests a new concept in cancer regulations. In addition, m6A‐targeted therapies including competitive antagonists of m6A‐associated proteins may provide a new tumour intervention in the future.

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Section: The Dual Role Of M6a Modification In Human Cancerssupporting

confidence: 53%

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Wang

et al. 2018

J Cellular Molecular Medi

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“…Most recently, a growing number of studies have reported that methylases and demethylases of m 6 A are correlated with cancer (8,30,38,39). As METTL3 is the core component of m 6 A the methyltransferase complex, we wondered whether SUMOylation of METTL3 is connected with tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Analysis of mRNA m 6 A methylation by dot-blotting was performed followed by a published procedure with minor changes (13,30). Briefly, total RNAs were isolated using the Trizol method and mRNAs were isolated by using GenElute™ mRNA Miniprep Kit (Sigma).…”

Section: Methodsmentioning

confidence: 99%

SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

Hou

Zhang

et al. 2018

Nucleic Acids Research

242

176

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The methyltransferase like 3 (METTL3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNAs including mRNA, tRNA, rRNA, small nuclear RNA, microRNA precursor and long non-coding RNA. However, the characteristics of METTL3 in activation and post-translational modification (PTM) is seldom understood. Here we find that METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1. SUMOylation of METTL3 does not alter its stability, localization and interaction with METTL14 and WTAP, but significantly represses its m6A methytransferase activity resulting in the decrease of m6A levels in mRNAs. Consistently with this, the abundance of m6A in mRNAs is increased with re-expression of the mutant METTL3-4KR compared to that of wild-type METTL3 in human non-small cell lung carcinoma (NSCLC) cell line H1299-shMETTL3, in which endogenous METTL3 was knockdown. The alternation of m6A in mRNAs and subsequently change of gene expression profiles, which are mediated by SUMOylation of METTL3, may directly influence the soft-agar colony formation and xenografted tumor growth of H1299 cells. Our results uncover an important mechanism for SUMOylation of METTL3 regulating its m6A RNA methyltransferase activity.

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“…Upon heat shock, YTHDF2 relocates to the nucleus, protects transcripts with m 6 A‐modified 5′UTR from demethylation by FTO and helps in cap‐independent translation initiation during stress conditions . A recent report on hepatocellular carcinoma demonstrated that increased levels of tumor suppressor miR‐145 degrades YTHDF2 and protects m 6 A‐containing RNA species . The contradicting function of these two proteins determines the final outcome of m 6 A targets.…”

Section: Decoders Of the M6a Markmentioning

confidence: 99%

mRNA Traffic Control Reviewed: N6‐Methyladenosine (m⁶A) Takes the Driver's Seat

Visvanathan

Somasundaram

2017

BioEssays

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Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since they are nonediting events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine (m 6 A) has gained the attention of RNA biologists. The m 6 A modification has a set of writers (methylases), erasers (demethylases), and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m 6 A epitranscriptome.

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MicroRNA-145 Modulates N6-Methyladenosine Levels by Targeting the 3′-Untranslated mRNA Region of the N6-Methyladenosine Binding YTH Domain Family 2 Protein

Abstract: Edited by Joel Gottesfeld

Cited by 231 publications

References 49 publications

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

mRNA Traffic Control Reviewed: N6‐Methyladenosine (m⁶A) Takes the Driver's Seat

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MicroRNA-145 Modulates N6-Methyladenosine Levels by Targeting the 3′-Untranslated mRNA Region of the N6-Methyladenosine Binding YTH Domain Family 2 Protein

Abstract: Edited by Joel Gottesfeld

Cited by 231 publications

References 49 publications

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function

mRNA Traffic Control Reviewed: N6‐Methyladenosine (m6A) Takes the Driver's Seat

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About

mRNA Traffic Control Reviewed: N6‐Methyladenosine (m⁶A) Takes the Driver's Seat