Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers

Molecular Cell, Journal Year: 2019, Volume and Issue: 74(4), P. 640 - 650

Published: May 1, 2019

Language: Английский

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The role of m6A RNA methylation in cancer

Biomedicine & Pharmacotherapy, Journal Year: 2019, Volume and Issue: 112, P. 108613 - 108613

Published: Feb. 19, 2019

N6-methyladenosine (m6A), the most abundant internal modification of RNA in eukaryotic cells, has gained increasing attention recent years. The m6A affects multiple aspects metabolism, ranging from processing, nuclear export, translation to decay. Emerging evidence suggests that methylation plays a critical role cancer through various mechanisms. Moreover, provided more possibilities for early diagnosis and treatment cancers. In this review, we focus on m6A-associated mechanisms functions several major malignancies summarize dual as well its prospects cancer.

Language: Английский

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Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(4), P. 677 - 691.e10

Published: April 1, 2019

Language: Английский

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m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: June 25, 2019

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N

Language: Английский

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m ⁶ A RNA methylation: from mechanisms to therapeutic potential

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(3)

Published: Jan. 20, 2021

Language: Английский

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The emerging role of RNA modifications in the regulation of mRNA stability

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(3), P. 400 - 408

Published: March 1, 2020

Many studies have highlighted the importance of tight regulation mRNA stability in control gene expression. largely depends on nucleotide sequence, which affects secondary and tertiary structures mRNAs, accessibility various RNA-binding proteins to mRNAs. Recent advances high-throughput RNA-sequencing techniques resulted elucidation important roles played by modifications sequences regulating stability. To date, hundreds different RNA been characterized. Among them, several modifications, including N

Language: Английский

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The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: 47(15), P. 7719 - 7733

Published: July 12, 2019

Abstract N6-methyladenosine (m6A) has recently been found abundantly on messenger RNA and shown to regulate most steps of mRNA metabolism. Several important m6A methyltransferases have described functionally structurally, but the enzymes responsible for installing one residue each subunit human ribosomes at sites eluded identification over 30 years. Here, we identify METTL5 as enzyme 18S rRNA modification confirm ZCCHC4 28S enzyme. We show that must form a heterodimeric complex with TRMT112, known methyltransferase activator, gain metabolic stability in cells. provide first atomic resolution structure METTL5–TRMT112, supporting its RNA-binding mode differs distinctly from other methyltransferases. On basis similarities DNA methyltransferase, propose METTL5–TRMT112 acts by extruding adenosine be modified double-stranded nucleic acid.

Language: Английский

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A comprehensive review of m6A/m6Am RNA methyltransferase structures

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(13), P. 7239 - 7255

Published: April 26, 2021

Abstract Gene expression is regulated at many levels including co- or post-transcriptionally, where chemical modifications are added to RNA on riboses and bases. Expression control via has been termed ‘epitranscriptomics’ keep with the related ‘epigenomics’ for DNA modification. One such modification N6-methylation found adenosine (m6A) 2′-O-methyladenosine (m6Am) in most types of RNA. The can affect fold, stability, degradation cellular interaction(s) modified RNA, implicating it processes as splicing, translation, export decay. multiple roles played by this explains why m6A misregulation connected human cancers. m6A/m6Am writer enzymes methyltransferases (MTases). Structures available functionally characterized MTases from (m6A mRNA, snRNA, rRNA m6Am mRNA MTases), zebrafish (m6Am MTase) bacteria MTase). For each these MTases, we describe their overall domain organization, active site architecture substrate binding. We identify areas that remain be investigated, propose yet unexplored routes structural characterization MTase:substrate complexes, highlight common elements should described future MTase structures.

Language: Английский

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The RNA modification N6-methyladenosine as a novel regulator of the immune system

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(5), P. 501 - 512

Published: April 13, 2020

Language: Английский

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RNA modifications regulating cell fate in cancer

Nature Cell Biology, Journal Year: 2019, Volume and Issue: 21(5), P. 552 - 559

Published: May 1, 2019

Language: Английский

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