Hidden codes in mRNA: Control of gene expression by m6A

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(12), P. 2236 - 2251

Published: June 1, 2022

Language: Английский

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RNA modifications in physiology and disease: towards clinical applications

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 104 - 122

Published: Sept. 15, 2023

Language: Английский

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The Proteins of mRNA Modification: Writers, Readers, and Erasers

Annual Review of Biochemistry, Journal Year: 2023, Volume and Issue: 92(1), P. 145 - 173

Published: April 17, 2023

Over the past decade, mRNA modifications have emerged as important regulators of gene expression control in cells. Fueled large part by development tools for detecting RNA transcriptome wide, researchers uncovered a diverse epitranscriptome that serves an additional layer regulation beyond simple sequence. Here, we review proteins write, read, and erase these marks, with particular focus on most abundant internal modification, N6-methyladenosine (m6A). We first describe discovery key enzymes deposit remove m6A other discuss how our understanding has shaped views modification dynamics. then current models function reader knowledge evolved. Finally, highlight future directions field questions remain unanswered.

Language: Английский

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Cryo-EM structures of human m6A writer complexes

Cell Research, Journal Year: 2022, Volume and Issue: 32(11), P. 982 - 994

Published: Sept. 27, 2022

Abstract N 6 -methyladenosine (m A) is the most abundant ribonucleotide modification among eukaryotic messenger RNAs. The m A “writer” consists of catalytic subunit A-METTL complex (MAC) and regulatory A-METTL-associated (MACOM), latter being essential for enzymatic activity. Here, we report cryo-electron microscopy (cryo-EM) structures MACOM at a 3.0-Å resolution, uncovering that WTAP VIRMA form core structure ZC3H13 stretches conformation by binding VIRMA. Furthermore, 4.4-Å resolution cryo-EM map MACOM–MAC complex, combined with crosslinking mass spectrometry GST pull-down analysis, elucidates plausible model writer in which binds to MAC mainly through METTL3 interactions. In combination vitro RNA substrate methyltransferase activity assays, our results illustrate molecular basis how assembles interacts an active complex.

Language: Английский

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Crosstalk between m6A modification and alternative splicing during cancer progression

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(10)

Published: Oct. 1, 2023

Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed demethylases and recognised m6A-binding proteins. This significantly influences carious facets of RNA metabolism plays a pivotal role cellular physiological processes. Main body Pre-mRNA alternative splicing, process that generates multiple splice isoforms from multi-exon genes, contributes to protein diversity mammals. Moreover, presence crosstalk between with modifications on pre-mRNAs exerting regulatory control, has been established. The modulates splicing patterns recruiting specific RNA-binding proteins (RBPs) regulate or directly influencing interaction RBPs their target RNAs. Conversely, can impact deposition recognition mRNAs. integration expanded scope therapeutic strategies for cancer treatment, while offers novel insights into mechanistic methylation initiation progression. Conclusion review aims highlight biological functions machinery its implications tumourigenesis. Furthermore, we discuss clinical relevance understanding m6A-dependent tumour therapies.

Language: Английский

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m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 15, 2023

Abstract Glycolytic reprogramming is one of the most important features cancer and plays an integral role in progression cancer. In cells, changes glucose metabolism meet needs self-proliferation, angiogenesis lymphangiogenesis, metastasis, also affect immune escape, prognosis evaluation therapeutic effect The n6-methyladenosine (m6A) modification RNA widespread eukaryotic cells. Dynamic reversible m6A modifications are widely involved regulation stem cell renewal differentiation, tumor therapy resistance, microenvironment, metabolism. Lately, more evidences show that can glycolysis process tumors a variety ways to regulate biological behavior tumors. this review, we discussed genesis development, elaborated detail profound impact on different by regulating glycolysis. We believe modified has great significance potential for treatment.

Language: Английский

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The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(8), P. 1208 - 1221

Published: July 25, 2022

Language: Английский

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Functional interdependence of N6-methyladenosine methyltransferase complex subunits in Arabidopsis

The Plant Cell, Journal Year: 2023, Volume and Issue: 35(6), P. 1901 - 1916

Published: March 9, 2023

Abstract Addition of N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is catalyzed by an evolutionarily conserved m6A methyltransferase complex. In model plant Arabidopsis thaliana, complex composed 2 core methyltransferases, adenosine methylase (MTA) and MTB, several accessory subunits such as FK506-BINDING PROTEIN 12 KD INTERACTING 37KD (FIP37), VIRILIZER (VIR), HAKAI. It yet largely unknown whether these influence functions MTA MTB. Herein, I reveal that FIP37 VIR are indispensable for stabilizing methyltransferases thus functioning key to maintain functionality Furthermore, affects HAKAI protein accumulation, while MTB mutually each other. contrast, has little effect on abundance or localization MTA, FIP37. These findings uncover unique functional interdependence at post-translational level among individual components complex, suggesting maintenance homeostasis various essential maintaining stoichiometry required proper function deposition plants.

Language: Английский

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Role of N6-methyladenosine modification in central nervous system diseases and related therapeutic agents

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114583 - 114583

Published: March 28, 2023

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. methylation RNA associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's (PD), depression, cerebral apoplexy, brain injury, epilepsy, arteriovenous malformations, glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns therapeutic areas disorders. Here, we mainly summarized role diseases potential drugs. The aim this review expected to be useful systematically assess as new biomarker develop innovative modulators for amelioration treatment

Language: Английский

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The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 126773 - 126773

Published: Sept. 9, 2023

Language: Английский

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